rs35110529
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_001018115.3(FANCD2):c.182C>T(p.Thr61Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000247 in 1,588,208 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts 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. T61T) has been classified as Likely benign.
Frequency
Consequence
NM_001018115.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCD2 | NM_001018115.3 | c.182C>T | p.Thr61Met | missense_variant | 3/44 | ENST00000675286.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCD2 | ENST00000675286.1 | c.182C>T | p.Thr61Met | missense_variant | 3/44 | NM_001018115.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000441 AC: 67AN: 152040Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000415 AC: 104AN: 250876Hom.: 0 AF XY: 0.000368 AC XY: 50AN XY: 135770
GnomAD4 exome AF: 0.000227 AC: 326AN: 1436050Hom.: 2 Cov.: 27 AF XY: 0.000218 AC XY: 156AN XY: 716106
GnomAD4 genome ? AF: 0.000440 AC: 67AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.000497 AC XY: 37AN XY: 74394
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 03, 2022 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Fanconi anemia Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Jun 19, 2021 | - - |
not specified Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 01, 2022 | DNA sequence analysis of the FANCD2 gene demonstrated a sequence change, c.182C>T, in exon 3 that results in an amino acid change, p.Thr61Met. This sequence change does not appear to have been previously described in individuals with FANCD2-related disorders. This sequence change has been described in the gnomAD database with a frequency of 0.4% in the Ashkenazi Jewish subpopulation (dbSNP rs35110529). The p.Thr61Met change affects a poorly conserved amino acid residue located in a domain of the FANCD2 protein that is not known to be functional. The p.Thr61Met substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Thr61Met change remains unknown at this time. - |
Fanconi anemia complementation group D2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Fanconi anemia complementation group A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
FANCD2-related condition Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 04, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at