rs3895942
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_001018115.3(FANCD2):c.2386-148G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 641,450 control chromosomes in the GnomAD database, including 12,306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.22 ( 4901 hom., cov: 32)
Exomes 𝑓: 0.16 ( 7405 hom. )
Consequence
FANCD2
NM_001018115.3 intron
NM_001018115.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0580
Genes affected
FANCD2 (HGNC:3585): (FA complementation group D2) The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group D2. This protein is monoubiquinated in response to DNA damage, resulting in its localization to nuclear foci with other proteins (BRCA1 AND BRCA2) involved in homology-directed DNA repair. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 3-10067061-G-C is Benign according to our data. Variant chr3-10067061-G-C is described in ClinVar as [Benign]. Clinvar id is 1259537.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FANCD2 | NM_001018115.3 | c.2386-148G>C | intron_variant | ENST00000675286.1 | NP_001018125.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FANCD2 | ENST00000675286.1 | c.2386-148G>C | intron_variant | NM_001018115.3 | ENSP00000502379.1 |
Frequencies
GnomAD3 genomes AF: 0.224 AC: 34042AN: 151814Hom.: 4896 Cov.: 32
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GnomAD4 exome AF: 0.163 AC: 79740AN: 489518Hom.: 7405 AF XY: 0.163 AC XY: 43117AN XY: 263736
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GnomAD4 genome AF: 0.224 AC: 34075AN: 151932Hom.: 4901 Cov.: 32 AF XY: 0.219 AC XY: 16229AN XY: 74248
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 11, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
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DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at