rs775898191
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001018115.3(FANCD2):c.4052C>T(p.Thr1351Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000706 in 1,613,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T1351T) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCD2 | NM_001018115.3 | c.4052C>T | p.Thr1351Met | missense_variant | 42/44 | ENST00000675286.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCD2 | ENST00000675286.1 | c.4052C>T | p.Thr1351Met | missense_variant | 42/44 | NM_001018115.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251422Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135886
GnomAD4 exome AF: 0.0000732 AC: 107AN: 1461766Hom.: 0 Cov.: 31 AF XY: 0.0000729 AC XY: 53AN XY: 727204
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74330
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2022 | FANCD2: BP4 - |
Fanconi anemia complementation group D2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 29, 2022 | - - |
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 29, 2022 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1351 of the FANCD2 protein (p.Thr1351Met). This variant is present in population databases (rs775898191, gnomAD 0.009%). 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: 456359). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine 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