rs397897610

chr3-10035158-C-CTchr3-10035158-CTTT-Cchr3-10035158-CT-Cchr3-10035158-CTT-Cchr3-10035158-C-CTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001018115.3(FANCD2):c.378-5dup variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0021 in 1,408,098 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000087 (0 hom., cov: 25)
  • Exomes 𝑓: 0.0023 (0 hom.)
• Consequence: FANCD2 NM_001018115.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FANCD2	NM_001018115.3	c.378-5dup		splice_polypyrimidine_tract_variant, intron_variant		ENST00000675286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCD2	ENST00000675286.1	c.378-5dup		splice_polypyrimidine_tract_variant, intron_variant			NM_001018115.3	P2

Frequencies

GnomAD3 genomes AF: 0.0000869 AC: 13 AN: 149610 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000668

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00117

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000200

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000447

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000904 AC: 164 AN: 181326 Hom.: 0 AF XY: 0.000819 AC XY: 80 AN XY: 97648

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000775

Gnomad ASJ exome AF: 0.00103

Gnomad EAS exome AF: 0.00136

Gnomad SAS exome AF: 0.000518

Gnomad FIN exome AF: 0.00434

Gnomad NFE exome AF: 0.000544

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.00235 AC: 2951 AN: 1258384 Hom.: 0 Cov.: 21 AF XY: 0.00215 AC XY: 1347 AN XY: 626724

Gnomad4 AFR exome AF: 0.000705

Gnomad4 AMR exome AF: 0.00107

Gnomad4 ASJ exome AF: 0.00144

Gnomad4 EAS exome AF: 0.00185

Gnomad4 SAS exome AF: 0.00112

Gnomad4 FIN exome AF: 0.00243

Gnomad4 NFE exome AF: 0.00260

Gnomad4 OTH exome AF: 0.00217

GnomAD4 genome AF: 0.0000868 AC: 13 AN: 149714 Hom.: 0 Cov.: 25 AF XY: 0.000137 AC XY: 10 AN XY: 73126

Gnomad4 AFR AF: 0.0000243

Gnomad4 AMR AF: 0.0000667

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00117

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000200

Gnomad4 NFE AF: 0.0000447

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs55973240; hg19: chr3-10076842;