3-10081346-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001018115.3(FANCD2):c.3106T>A(p.Cys1036Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001018115.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FANCD2 | NM_001018115.3 | c.3106T>A | p.Cys1036Ser | missense_variant, splice_region_variant | 32/44 | ENST00000675286.1 | NP_001018125.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FANCD2 | ENST00000675286.1 | c.3106T>A | p.Cys1036Ser | missense_variant, splice_region_variant | 32/44 | NM_001018115.3 | ENSP00000502379 | P2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251376Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135848
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461108Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726924
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 28, 2021 | This sequence change replaces cysteine with serine at codon 1036 of the FANCD2 protein (p.Cys1036Ser). The cysteine residue is weakly conserved and there is a moderate physicochemical difference between cysteine and serine. This variant is present in population databases (rs767901156, ExAC 0.03%). This variant has not been reported in the literature in individuals affected with FANCD2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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