rs6807485

Positions:

• chr3-10092636-C-G
• chr3-10092636-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001018115.3(FANCD2):​c.3849+384C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 149,890 control chromosomes in the GnomAD database, including 1,700 homozygotes. 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 0.12 (1700 hom., cov: 27)
• Consequence: FANCD2 NM_001018115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129

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]

FANCD2OS (HGNC:28623): (FANCD2 opposite strand) This gene encodes a conserved protein of unknown function. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCD2	NM_001018115.3	c.3849+384C>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.3849+384C>G		intron_variant			NM_001018115.3	ENSP00000502379	P2

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18410 AN: 149786 Hom.: 1698 Cov.: 27

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.0374

Gnomad AMR AF: 0.0757

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.000978

Gnomad SAS AF: 0.0192

Gnomad FIN AF: 0.0568

Gnomad MID AF: 0.0774

Gnomad NFE AF: 0.0784

Gnomad OTH AF: 0.111

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.123 AC: 18423 AN: 149890 Hom.: 1700 Cov.: 27 AF XY: 0.120 AC XY: 8752 AN XY: 73050

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.0755

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.000980

Gnomad4 SAS AF: 0.0190

Gnomad4 FIN AF: 0.0568

Gnomad4 NFE AF: 0.0784

Gnomad4 OTH AF: 0.110

Alfa AF: 0.100 Hom.: 145

Bravo AF: 0.131

Asia WGS AF: 0.0230 AC: 80 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.38

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: rs6807485; hg19: chr3-10134320;