BRCA1 deletion exon1 and 2

[Paolo Tarantino]

Dear HGVS support,
I have a question about the nomenclature of 5' UTR deletion (exon1) in the BRCA1 gene.
I have detected by NGS a large rearrangement incomprise of exon 1 and exon 2 of BRCA1.

I know that the breaking point in intron 2 is unknown and nomenclature is (......)_(80+1_80-1)del.
The problem is in the region 5' UTR.

The exon1 of BRCA1 is a 5'UTR and the unknown breaking point  is in the 5' flanking sequence.
But I don't know how to describe it.

Please look at the attached image.

Best regards

Paolo

--

Dott. Paolo Tarantino

Dirigente Biologo

U.O.C. Genetica Medica  

P.O. Vito Fazzi, ASL Lecce

Piazza F.Muratore, 1

73100 Lecce

Tel: 0832.661290

[Ivo Fokkema]

Dear Paolo,

From the documentation on deletions on DNA level:

• deletions extending beyond the transcribed regionfollowing current recommendations (see Numbering) it is not allowed to describe variants in nucleotides beyond the boundaries of a reference sequence. Consequently, deletions extending 5’ of a transcript can not be described like NC_000023.11(NM_004006.2):c.(?_-244)_(31+1_32-1)del (c.-244 is the first nucleotide of NM_004006.2). Deletions extending 3’ of a transcript can not be described like NC_000023.11(NM_004006.2):c.(10086+1_10087-1)_(*2691_?)del (c.*2691 is the last nucleotide of NM_004006.2). Such deletions can only be described using genomic coordinates. The HGVS nomenclature committee (SVD-WG) is discussing whether a c. based format should be proposed.

Source: https://varnomen.hgvs.org/recommendations/DNA/variant/deletion/

As you can read above, the HVNC (HGVS Variant Nomenclature Committee) still needs to decide on what syntax is acceptable for the transcript level.
NC_000017.10(NM_007294.3):c.?_(80+1_81-1)del or NC_000017.10(NM_007294.3):c.(?_-232)_(80+1_81-1)del can not officially be used, and currently, the variant can only be described on the genomic level. Assuming that you have confirmed that exon 1 has been deleted, on the genomic level the variant should be described as NC_000017.10:g.(41267797_41276033)_(41277500_?)del (this assumes hg19/GRCh37).