chr13-32315562-T-TGCCGTCTTTTAGCATACAGGTCTTGTGCAGCTTTTATCAGATTTCTTCCTCTAAGTCTTGATACTTTTTTTTTTTTTAATAATACTTTAAGTTCCGCAATACATGTGCAGAACCTGCAGGTTTGTTACATAGGTATACACGTGCCATGGTGGTTTGCTACACCCATCAACCTGTCATCTACATTAGATATTTCTCCTAATGCTATCCCTTCCCTAGCCCCCCATCCCCCAATAGCCCCCGGTGTGTGATGTTCCCTGCCCTGTGTCCACGTGTTCTCATTGTTCAACTCCCACTTATCAGTGAGAACACGCGGTGTTTGTTTTTCTGTTCTCGTGTTATTTTTCTGAGAATGATATGGTTTCCAGCTTCATCCATGTCCCTGCAAAGGACATGAACTCATTCTTTTTTATGGCCACATAGTATTCTGTGGTGTATATGGGCCACATTTTCTTTATCCAGTCTATCATTGATGGGCATTTGGGTAGGTTCCAAGTCTTTGCTAATTTTGAAATTATCATTTCACAGCTTAATTTCTGATGGTTCCTTGCTAGTATTTAGAAATACAATTGATTTTTTTATGTTGATCTTAAAAAATTGCAAGCTTACCTATCTTGTTTATTAGATCTAGTAACTTATTTGTAGATTCCATTGGGTTTTCTACAAATAGACTCATGTTGCCTAAGAATAAAGGCTTACTTTTTTCCCACTATGAATCCTTTTTATTTGTATTTTTTTCCTTGCCTTATTGCACTGGCTAGAATCTAAAGTATAATGTTGAACAGACATGGTGAGAGCAGATATTCTTACAACTGACCCACACTTAGGTTTGTGGAGAAAGCACTCAGTCTTTCACCATTAAGTATGTTAACTGTACTTAGTTAACTGTAGG

Position:

• chr13-32315562-T-TGCCGTCTTTTAGCATACAGGTCTTGTGCAGCTTTTATCAGATTTCTTCCTCTAAGTCTTGATACTTTTTTTTTTTTTAATAATACTTTAAGTTCCGCAATACATGTGCAGAACCTGCAGGTTTGTTACATAGGTATACACGTGCCATGGTGGTTTGCTACACCCATCAACCTGTCATCTACATTAGATATTTCTCCTAATGCTATCCCTTCCCTAGCCCCCCATCCCCCAATAGCCCCCGGTGTGTGATGTTCCCTGCCCTGTGTCCACGTGTTCTCATTGTTCAACTCCCACTTATCAGTGAGAACACGCGGTGTTTGTTTTTCTGTTCTCGTGTTATTTTTCTGAGAATGATATGGTTTCCAGCTTCATCCATGTCCCTGCAAAGGACATGAACTCATTCTTTTTTATGGCCACATAGTATTCTGTGGTGTATATGGGCCACATTTTCTTTATCCAGTCTATCATTGATGGGCATTTGGGTAGGTTCCAAGTCTTTGCTAATTTTGAAATTATCATTTCACAGCTTAATTTCTGATGGTTCCTTGCTAGTATTTAGAAATACAATTGATTTTTTTATGTTGATCTTAAAAAATTGCAAGCTTACCTATCTTGTTTATTAGATCTAGTAACTTATTTGTAGATTCCATTGGGTTTTCTACAAATAGACTCATGTTGCCTAAGAATAAAGGCTTACTTTTTTCCCACTATGAATCCTTTTTATTTGTATTTTTTTCCTTGCCTTATTGCACTGGCTAGAATCTAAAGTATAATGTTGAACAGACATGGTGAGAGCAGATATTCTTACAACTGACCCACACTTAGGTTTGTGGAGAAAGCACTCAGTCTTTCACCATTAAGTATGTTAACTGTACTTAGTTAACTGTAGG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000059.4(BRCA2):​c.-143_-142insCGTCTTTTAGCATACAGGTCTTGTGCAGCTTTTATCAGATTTCTTCCTCTAAGTCTTGATACTTTTTTTTTTTTTAATAATACTTTAAGTTCCGCAATACATGTGCAGAACCTGCAGGTTTGTTACATAGGTATACACGTGCCATGGTGGTTTGCTACACCCATCAACCTGTCATCTACATTAGATATTTCTCCTAATGCTATCCCTTCCCTAGCCCCCCATCCCCCAATAGCCCCCGGTGTGTGATGTTCCCTGCCCTGTGTCCACGTGTTCTCATTGTTCAACTCCCACTTATCAGTGAGAACACGCGGTGTTTGTTTTTCTGTTCTCGTGTTATTTTTCTGAGAATGATATGGTTTCCAGCTTCATCCATGTCCCTGCAAAGGACATGAACTCATTCTTTTTTATGGCCACATAGTATTCTGTGGTGTATATGGGCCACATTTTCTTTATCCAGTCTATCATTGATGGGCATTTGGGTAGGTTCCAAGTCTTTGCTAATTTTGAAATTATCATTTCACAGCTTAATTTCTGATGGTTCCTTGCTAGTATTTAGAAATACAATTGATTTTTTTATGTTGATCTTAAAAAATTGCAAGCTTACCTATCTTGTTTATTAGATCTAGTAACTTATTTGTAGATTCCATTGGGTTTTCTACAAATAGACTCATGTTGCCTAAGAATAAAGGCTTACTTTTTTCCCACTATGAATCCTTTTTATTTGTATTTTTTTCCTTGCCTTATTGCACTGGCTAGAATCTAAAGTATAATGTTGAACAGACATGGTGAGAGCAGATATTCTTACAACTGACCCACACTTAGGTTTGTGGAGAAAGCACTCAGTCTTTCACCATTAAGTATGTTAACTGTACTTAGTTAACTGTAGGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BRCA2 NM_000059.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.757

Genes affected

BRCA2 (HGNC:1101): (BRCA2 DNA repair associated) Inherited mutations in BRCA1 and this gene, BRCA2, confer increased lifetime risk of developing breast or ovarian cancer. Both BRCA1 and BRCA2 are involved in maintenance of genome stability, specifically the homologous recombination pathway for double-strand DNA repair. The largest exon in both genes is exon 11, which harbors the most important and frequent mutations in breast cancer patients. The BRCA2 gene was found on chromosome 13q12.3 in human. The BRCA2 protein contains several copies of a 70 aa motif called the BRC motif, and these motifs mediate binding to the RAD51 recombinase which functions in DNA repair. BRCA2 is considered a tumor suppressor gene, as tumors with BRCA2 mutations generally exhibit loss of heterozygosity (LOH) of the wild-type allele. [provided by RefSeq, May 2020]

BRCA2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRCA2	NM_000059.4	c.-143_-142insCGTCTTTTAGCATACAGGTCTTGTGCAGCTTTTATCAGATTTCTTCCTCTAAGTCTTGATACTTTTTTTTTTTTTAATAATACTTTAAGTTCCGCAATACATGTGCAGAACCTGCAGGTTTGTTACATAGGTATACACGTGCCATGGTGGTTTGCTACACCCATCAACCTGTCATCTACATTAGATATTTCTCCTAATGCTATCCCTTCCCTAGCCCCCCATCCCCCAATAGCCCCCGGTGTGTGATGTTCCCTGCCCTGTGTCCACGTGTTCTCATTGTTCAACTCCCACTTATCAGTGAGAACACGCGGTGTTTGTTTTTCTGTTCTCGTGTTATTTTTCTGAGAATGATATGGTTTCCAGCTTCATCCATGTCCCTGCAAAGGACATGAACTCATTCTTTTTTATGGCCACATAGTATTCTGTGGTGTATATGGGCCACATTTTCTTTATCCAGTCTATCATTGATGGGCATTTGGGTAGGTTCCAAGTCTTTGCTAATTTTGAAATTATCATTTCACAGCTTAATTTCTGATGGTTCCTTGCTAGTATTTAGAAATACAATTGATTTTTTTATGTTGATCTTAAAAAATTGCAAGCTTACCTATCTTGTTTATTAGATCTAGTAACTTATTTGTAGATTCCATTGGGTTTTCTACAAATAGACTCATGTTGCCTAAGAATAAAGGCTTACTTTTTTCCCACTATGAATCCTTTTTATTTGTATTTTTTTCCTTGCCTTATTGCACTGGCTAGAATCTAAAGTATAATGTTGAACAGACATGGTGAGAGCAGATATTCTTACAACTGACCCACACTTAGGTTTGTGGAGAAAGCACTCAGTCTTTCACCATTAAGTATGTTAACTGTACTTAGTTAACTGTAGGGC		5_prime_UTR_variant	1/27	ENST00000380152.8	NP_000050.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRCA2	ENST00000380152	c.-143_-142insCGTCTTTTAGCATACAGGTCTTGTGCAGCTTTTATCAGATTTCTTCCTCTAAGTCTTGATACTTTTTTTTTTTTTAATAATACTTTAAGTTCCGCAATACATGTGCAGAACCTGCAGGTTTGTTACATAGGTATACACGTGCCATGGTGGTTTGCTACACCCATCAACCTGTCATCTACATTAGATATTTCTCCTAATGCTATCCCTTCCCTAGCCCCCCATCCCCCAATAGCCCCCGGTGTGTGATGTTCCCTGCCCTGTGTCCACGTGTTCTCATTGTTCAACTCCCACTTATCAGTGAGAACACGCGGTGTTTGTTTTTCTGTTCTCGTGTTATTTTTCTGAGAATGATATGGTTTCCAGCTTCATCCATGTCCCTGCAAAGGACATGAACTCATTCTTTTTTATGGCCACATAGTATTCTGTGGTGTATATGGGCCACATTTTCTTTATCCAGTCTATCATTGATGGGCATTTGGGTAGGTTCCAAGTCTTTGCTAATTTTGAAATTATCATTTCACAGCTTAATTTCTGATGGTTCCTTGCTAGTATTTAGAAATACAATTGATTTTTTTATGTTGATCTTAAAAAATTGCAAGCTTACCTATCTTGTTTATTAGATCTAGTAACTTATTTGTAGATTCCATTGGGTTTTCTACAAATAGACTCATGTTGCCTAAGAATAAAGGCTTACTTTTTTCCCACTATGAATCCTTTTTATTTGTATTTTTTTCCTTGCCTTATTGCACTGGCTAGAATCTAAAGTATAATGTTGAACAGACATGGTGAGAGCAGATATTCTTACAACTGACCCACACTTAGGTTTGTGGAGAAAGCACTCAGTCTTTCACCATTAAGTATGTTAACTGTACTTAGTTAACTGTAGGGC		5_prime_UTR_variant	1/27	5	NM_000059.4	ENSP00000369497.3
BRCA2	ENST00000530893	c.-508_-507insCGTCTTTTAGCATACAGGTCTTGTGCAGCTTTTATCAGATTTCTTCCTCTAAGTCTTGATACTTTTTTTTTTTTTAATAATACTTTAAGTTCCGCAATACATGTGCAGAACCTGCAGGTTTGTTACATAGGTATACACGTGCCATGGTGGTTTGCTACACCCATCAACCTGTCATCTACATTAGATATTTCTCCTAATGCTATCCCTTCCCTAGCCCCCCATCCCCCAATAGCCCCCGGTGTGTGATGTTCCCTGCCCTGTGTCCACGTGTTCTCATTGTTCAACTCCCACTTATCAGTGAGAACACGCGGTGTTTGTTTTTCTGTTCTCGTGTTATTTTTCTGAGAATGATATGGTTTCCAGCTTCATCCATGTCCCTGCAAAGGACATGAACTCATTCTTTTTTATGGCCACATAGTATTCTGTGGTGTATATGGGCCACATTTTCTTTATCCAGTCTATCATTGATGGGCATTTGGGTAGGTTCCAAGTCTTTGCTAATTTTGAAATTATCATTTCACAGCTTAATTTCTGATGGTTCCTTGCTAGTATTTAGAAATACAATTGATTTTTTTATGTTGATCTTAAAAAATTGCAAGCTTACCTATCTTGTTTATTAGATCTAGTAACTTATTTGTAGATTCCATTGGGTTTTCTACAAATAGACTCATGTTGCCTAAGAATAAAGGCTTACTTTTTTCCCACTATGAATCCTTTTTATTTGTATTTTTTTCCTTGCCTTATTGCACTGGCTAGAATCTAAAGTATAATGTTGAACAGACATGGTGAGAGCAGATATTCTTACAACTGACCCACACTTAGGTTTGTGGAGAAAGCACTCAGTCTTTCACCATTAAGTATGTTAACTGTACTTAGTTAACTGTAGGGC		5_prime_UTR_variant	1/27	1		ENSP00000499438.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary breast ovarian cancer syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 28, 2023

This variant occurs in a non-coding region of the BRCA2 gene. It does not change the encoded amino acid sequence of the BRCA2 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-32889699;