NM_007294.4:c.2574G>A
Variant summary
Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_007294.4(BRCA1):c.2574G>A(p.Gln858Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_007294.4 synonymous
Scores
Clinical Significance
Conservation
Publications
- breast-ovarian cancer, familial, susceptibility to, 1Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
- Fanconi anemia, complementation group SInheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
- pancreatic cancer, susceptibility to, 4Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
- hereditary breast ovarian cancer syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Fanconi anemiaInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Benign. The variant received -9 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461330Hom.: 0 Cov.: 42 AF XY: 0.00000413 AC XY: 3AN XY: 726908 show subpopulations
Age Distribution
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:2
PM2_Supporting, BP1_Strong c.2574G>A, located outside any (potentially) clinically important functional domain of BRCA1, is predicted to result in no splicing alteration (according to SpliceAI) and no amino acid change, p.(Gln858=) (BP1_Strong). It is not present in the population database gnomAD v2.1.1, non cancer dataset (PM2_supporting). To our knowledge, neither relevant clinical data nor well-stablished functional studies have been reported for this variant. The variant has been reported in ClinVar** (2x likely benign). Based on currently available information, the variant c.2574G>A should be considered a likely benign variant. -
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not specified Benign:1
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Hereditary breast ovarian cancer syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at