URGENT - Question about HGVS nomenclature

[Ana Margarida Coutinho]

Dear Sirs,

We found by NGS 3 variants in cis in the gene SH3PXD2B (NM_001017995.3), 2 deletions (likely pathogenic) and 1 SNV (VUS), all of them separated my more than one nucleotide:

• c.958_964del p.(Gln320Thrfs*21) 
• c.967G>C p.(Gly323Arg) 
• c.970_971del p.(Arg324Valfs*2)

My questions is: according to HGVS, these variants should be described separately or together as a delins?

If they are described as a unique delins, it stays (VUS):

• c.958_970delinsACCG p.(Gln320_Arg324delinsThrGly)

Thank you very much in advance for your help.

Best regards,

Os melhores cumprimentos,  ___

Ana Coutinho, PhD Geneticista Molecular

___ Laboratório Central de Lisboa Pólo Tecnológico de Lisboa Rua Cupertino de Miranda, 9 - lote 8 - 1600-513 Lisboa tlf: 800 209 498

www.germanodesousa.com

[j.f.j.laros]

Dear Ana Margarida Coutinho,

NM_001017995.3:c.958_970delinsACCG

Thank you for your question.

Since the variants you have found are in cis, they should be described together in order to obtain correct effect predictions down the line. In HGVS, the allele syntax can be used for this.

In your case,  a description like NM_001017995.3:c.[958_964del;967G>C;970_971del] would be fine, leading to the predicted protein effect: NP_001017995.1:p.(Gln320_Arg324delinsThrGly), which indeed seems to be a lot milder at first glance than any of the single frame shift inducing variants.

Please note that Mutalyzer (see link above) normalises this allele description to NM_001017995.3:c.958_970delinsACCG. If you are interested in the motivation behind this normalisation, please feel free to ask.

With kind regards,

Jeroen

[Ana Margarida Coutinho]

Dear Prof. Johan den Dunnen,

Thank you for your reply.

Best regards,

Os melhores cumprimentos,  ___

Ana Coutinho, PhD Geneticista Molecular

___ Laboratório Central de Lisboa Pólo Tecnológico de Lisboa Rua Cupertino de Miranda, 9 - lote 8 - 1600-513 Lisboa tlf: 800 209 498

www.germanodesousa.com

---

De: JT den Dunnen <ddu...@humgen.nl>
Enviado: 30 de janeiro de 2026 14:17
Para: Ana Margarida Coutinho <ana.co...@germanodesousa.com>
Cc: Yuri Chiodo <yuri....@germanodesousa.com>; hgvs-nom...@googlegroups.com <hgvs-nom...@googlegroups.com>
Assunto: Re: URGENT - Question about HGVS nomenclature

 

Aviso de Segurança: Este email teve origem fora da organização. Não clique em hiperligações, ou anexos, se não conhecer o remetente ou não estiver certo de que o conteúdo é seguro. Em caso de dúvida reporte o email suspeito para análise.

Dear Ana,

following current recommendations the variant can be described as
NC_000005.10:g.[172350405_172350406del;172350408C>G;172350411_172350417del]

NM_001017995.3:c.[958_964del;967G>C;970_971del]

p.(Gln320_Arg324delinsThrGly).

Alternatively you can describe the variant as

NC_000005.10:g.172350405_172350417delinsCGGT
NM_001017995.3:c.958_970delinsACCG

so also on DNA level as 1 variant.

Please note that HGVS nomenclature demands that all variants are
described at genomic level, descriptions at other levels may be added.

Please note that you can NOT describe the predicted consequences at the
protein level as p.(Gln320Thrfs*21), p.(Gly323Arg) and
p.(Arg324Valfs*2). They are all wrong, you know the individual variants
at DNA level effect the subsequent consequences at protein level.

Best regards,

        Johan den Dunnen
        HUGO HGVS Variant Nomenclature Committee (HVNC)



Op 26-01-2026 om 12:30 schreef Ana Margarida Coutinho:
>
> Dear Sirs,
>
> We found by NGS 3 variants in /cis /in the gene /SH3PXD2B /

> (NM_001017995.3), 2 deletions (likely pathogenic) and 1 SNV (VUS), all
> of them separated my more than one nucleotide:
>

>   *
>     c.958_964del p.(Gln320Thrfs*21)
>   *
>     c.967G>C p.(Gly323Arg)
>   *

>     c.970_971del p.(Arg324Valfs*2)
>
>
> My questions is: according to HGVS, these variants should be described
> separately or together as a delins?
>
> If they are described as a unique delins, it stays (VUS):
>

>   *

>     c.958_970delinsACCG p.(Gln320_Arg324delinsThrGly)
>
>
>
> Thank you very much in advance for your help.
> Best regards,
>
>

> *Os melhores cumprimentos,*
>
> ___
>
> *Ana Coutinho, PhD*
> *Geneticista Molecular*
>
> ___
>
> *Laboratório Central de Lisboa*
> *Pólo Tecnológico de Lisboa*
> *Rua Cupertino de Miranda, 9 - lote 8 - 1600-513 Lisboa <https://eur04.safelinks.protection.outlook.com/?url=https%3A%2F%2Fg.page%2F&data=05%7C02%7Cana.coutinho%40germanodesousa.com%7C2c87461391c04c62f2d808de600a5675%7C21a3e473ce3b44e98342009c39ec9319%7C0%7C0%7C639053794700093673%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=uogaReHvvR1IjYY5Woqe%2BVjZUu4yiaBEtan6Ykbi8j4%3D&reserved=0
> LaboratorioCentralGermanodeSousa?share>*
> *tlf: 800 209 498*
>
> https://eur04.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.germanodesousa.com%2F&data=05%7C02%7Cana.coutinho%40germanodesousa.com%7C2c87461391c04c62f2d808de600a5675%7C21a3e473ce3b44e98342009c39ec9319%7C0%7C0%7C639053794700135659%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=b5MdBMw5UO3EpkeOaJx2jfPj9a2RVp8%2Flu5Txy%2FzHDQ%3D&reserved=0 <https://eur04.safelinks.protection.outlook.com/?url=https%3A%2F%2Fwww.germanodesousa.com%2F&data=05%7C02%7Cana.coutinho%40germanodesousa.com%7C2c87461391c04c62f2d808de600a5675%7C21a3e473ce3b44e98342009c39ec9319%7C0%7C0%7C639053794700175136%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=g8Ss9tFgo%2FIw%2FpYQE9YzyzX%2FR5abCK1yvcwOUtWg0sI%3D&reserved=0> Facebook icon
> <https://eur04.safelinks.protection.outlook.com/?url=https%3A%2F%2Fwww.facebook.com%2F&data=05%7C02%7Cana.coutinho%40germanodesousa.com%7C2c87461391c04c62f2d808de600a5675%7C21a3e473ce3b44e98342009c39ec9319%7C0%7C0%7C639053794700212054%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=DlfWJ2wgVvoZekcgOLdz6Qn3DaJYpdYM41oId1WpaQQ%3D&reserved=0
> GermanoDeSousaCentroDeMedicinaLaboratorial>LinkedIn icon <https://
> https://eur04.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.linkedin.com%2Fcompany%2Fgrupogermanosousa%2F&data=05%7C02%7Cana.coutinho%40germanodesousa.com%7C2c87461391c04c62f2d808de600a5675%7C21a3e473ce3b44e98342009c39ec9319%7C0%7C0%7C639053794700244720%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=l0zxgfCiE27xq4rNpGWKX67XPXVG5xcyuPxpPTvDmj0%3D&reserved=0>Instagram icon <https://
> https://eur04.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.instagram.com%2Fgrupogermanodesousa%2F&data=05%7C02%7Cana.coutinho%40germanodesousa.com%7C2c87461391c04c62f2d808de600a5675%7C21a3e473ce3b44e98342009c39ec9319%7C0%7C0%7C639053794700273728%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=i8NsHygkuUVAvM%2Fcp0T9Xg51qbiMfq5NUM2JKNvqb3w%3D&reserved=0>Youtbue icon <https://
> https://eur04.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.youtube.com%2Fchannel%2FUCCKpNxL9gkRRLieL3KkdgMQ%2F&data=05%7C02%7Cana.coutinho%40germanodesousa.com%7C2c87461391c04c62f2d808de600a5675%7C21a3e473ce3b44e98342009c39ec9319%7C0%7C0%7C639053794700301950%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=xkj1Y05LRsHE4grZlKr5ioP0yMbOaWv3SjHFvYl94oc%3D&reserved=0>
>
>
>
>

[JT den Dunnen]

Dear Ana,

following current recommendations the variant can be described as
NC_000005.10:g.[172350405_172350406del;172350408C>G;172350411_172350417del]
NM_001017995.3:c.[958_964del;967G>C;970_971del]
p.(Gln320_Arg324delinsThrGly).

Alternatively you can describe the variant as

NC_000005.10:g.172350405_172350417delinsCGGT
NM_001017995.3:c.958_970delinsACCG

so also on DNA level as 1 variant.

Please note that HGVS nomenclature demands that all variants are
described at genomic level, descriptions at other levels may be added.

Please note that you can NOT describe the predicted consequences at the
protein level as p.(Gln320Thrfs*21), p.(Gly323Arg) and
p.(Arg324Valfs*2). They are all wrong, you know the individual variants
at DNA level effect the subsequent consequences at protein level.

Best regards,

Johan den Dunnen
HUGO HGVS Variant Nomenclature Committee (HVNC)



Op 26-01-2026 om 12:30 schreef Ana Margarida Coutinho:
>

> Dear Sirs,
>
> We found by NGS 3 variants in /cis /in the gene /SH3PXD2B /

> (NM_001017995.3), 2 deletions (likely pathogenic) and 1 SNV (VUS), all
> of them separated my more than one nucleotide:
>

> *
> c.958_964del p.(Gln320Thrfs*21)
> *
> c.967G>C p.(Gly323Arg)
> *

> c.970_971del p.(Arg324Valfs*2)
>
>
> My questions is: according to HGVS, these variants should be described
> separately or together as a delins?
>
> If they are described as a unique delins, it stays (VUS):
>

> *

> c.958_970delinsACCG p.(Gln320_Arg324delinsThrGly)
>
>
>
> Thank you very much in advance for your help.
> Best regards,
>
>

> *Os melhores cumprimentos,*
>
> ___
>
> *Ana Coutinho, PhD*
> *Geneticista Molecular*
>
> ___
>
> *Laboratório Central de Lisboa*
> *Pólo Tecnológico de Lisboa*

> *Rua Cupertino de Miranda, 9 - lote 8 - 1600-513 Lisboa <https://g.page/

> LaboratorioCentralGermanodeSousa?share>*
> *tlf: 800 209 498*
>

> www.germanodesousa.com <https://www.germanodesousa.com/> Facebook icon
> <https://www.facebook.com/

> GermanoDeSousaCentroDeMedicinaLaboratorial>LinkedIn icon <https://

> www.linkedin.com/company/grupogermanosousa/>Instagram icon <https://
> www.instagram.com/grupogermanodesousa/>Youtbue icon <https://
> www.youtube.com/channel/UCCKpNxL9gkRRLieL3KkdgMQ/>
>
>
>
>