3-10048089-A-G

Position:

• chr3-10048089-A-G

Variant summary

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

The NM_001018115.3(FANCD2):​c.1413+38A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.43 (0 hom., cov: 47)
  • Exomes 𝑓: 0.33 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FANCD2 NM_001018115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.402

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=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCD2	NM_001018115.3	c.1413+38A>G		intron_variant		ENST00000675286.1	NP_001018125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCD2	ENST00000675286.1	c.1413+38A>G		intron_variant			NM_001018115.3	ENSP00000502379	P2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 60252 AN: 140926 Hom.: 0 Cov.: 47 FAILED QC

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.413

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.423

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.330 AC: 367961 AN: 1114936 Hom.: 0 Cov.: 44 AF XY: 0.335 AC XY: 187661 AN XY: 560656

Gnomad4 AFR exome AF: 0.362

Gnomad4 AMR exome AF: 0.348

Gnomad4 ASJ exome AF: 0.387

Gnomad4 EAS exome AF: 0.358

Gnomad4 SAS exome AF: 0.321

Gnomad4 FIN exome AF: 0.441

Gnomad4 NFE exome AF: 0.318

Gnomad4 OTH exome AF: 0.355

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.428 AC: 60300 AN: 141044 Hom.: 0 Cov.: 47 AF XY: 0.427 AC XY: 29443 AN XY: 68896

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.423

Alfa AF: 0.0685 Hom.: 845

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.4
DANN	Benign	0.46

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: rs7615646; hg19: chr3-10089773; COSMIC: COSV55031871; COSMIC: COSV55031871;