rs56350437

chr3-10043722-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001018115.3(FANCD2):c.1099-107G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0061 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0076 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: FANCD2 NM_001018115.3 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.628

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FANCD2	NM_001018115.3	c.1099-107G>T		intron_variant		ENST00000675286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCD2	ENST00000675286.1	c.1099-107G>T		intron_variant			NM_001018115.3	P2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 792 AN: 130220 Hom.: 0 Cov.: 33 FAILED QC

Gnomad AFR AF: 0.0101

Gnomad AMI AF: 0.00865

Gnomad AMR AF: 0.00734

Gnomad ASJ AF: 0.00164

Gnomad EAS AF: 0.00260

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.00493

Gnomad MID AF: 0.00368

Gnomad NFE AF: 0.00373

Gnomad OTH AF: 0.00437

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00757 AC: 7359 AN: 972122 Hom.: 1 Cov.: 15 AF XY: 0.00809 AC XY: 3996 AN XY: 493720

Gnomad4 AFR exome AF: 0.00869

Gnomad4 AMR exome AF: 0.00835

Gnomad4 ASJ exome AF: 0.00649

Gnomad4 EAS exome AF: 0.00501

Gnomad4 SAS exome AF: 0.0120

Gnomad4 FIN exome AF: 0.00332

Gnomad4 NFE exome AF: 0.00756

Gnomad4 OTH exome AF: 0.00634

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00610 AC: 795 AN: 130334 Hom.: 0 Cov.: 33 AF XY: 0.00619 AC XY: 396 AN XY: 63974

Gnomad4 AFR AF: 0.0101

Gnomad4 AMR AF: 0.00733

Gnomad4 ASJ AF: 0.00164

Gnomad4 EAS AF: 0.00261

Gnomad4 SAS AF: 0.0111

Gnomad4 FIN AF: 0.00493

Gnomad4 NFE AF: 0.00374

Gnomad4 OTH AF: 0.00431

Alfa AF: 0.0141 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 29, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.15
Dann	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs56350437; hg19: chr3-10085406;