chr3-10065966-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001018115.3(FANCD2):āc.2372A>Gā(p.Asn791Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,604,192 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. N791N) has been classified as Likely benign.
Frequency
Consequence
NM_001018115.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCD2 | NM_001018115.3 | c.2372A>G | p.Asn791Ser | missense_variant | 25/44 | ENST00000675286.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCD2 | ENST00000675286.1 | c.2372A>G | p.Asn791Ser | missense_variant | 25/44 | NM_001018115.3 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152134Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000637 AC: 16AN: 251042Hom.: 0 AF XY: 0.0000737 AC XY: 10AN XY: 135670
GnomAD4 exome AF: 0.00000826 AC: 12AN: 1451940Hom.: 0 Cov.: 28 AF XY: 0.0000124 AC XY: 9AN XY: 722972
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152252Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74446
ClinVar
Submissions by phenotype
not specified Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 27, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 15, 2024 | Variant summary: FANCD2 c.2372A>G (p.Asn791Ser) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.1e-05 in 1604192 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in FANCD2 causing Fanconi Anemia (1.1e-05 vs 0.00048), allowing no conclusion about variant significance. c.2372A>G has been reported in the literature in an individual affected with Fanconi Anemia (Chang_2023). This report does not provide unequivocal conclusions about association of the variant with Fanconi Anemia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 36463940). ClinVar contains an entry for this variant (Variation ID: 435145). Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Fanconi anemia complementation group D2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 05, 2022 | - - |
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 791 of the FANCD2 protein (p.Asn791Ser). This variant is present in population databases (rs758718558, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with FANCD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 435145). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FANCD2 protein function. 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at