3-10026743-GCCAGATGGTA-G

Position:

• chr3-10026743-GCCAGATGGTA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001018115.3(FANCD2):​c.-34+271_-34+280delCCAGATGGTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,136 control chromosomes in the GnomAD database, including 3,369 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3368 hom., cov: 27)
  • Exomes 𝑓: 0.14 (1 hom.)
• Consequence: FANCD2 NM_001018115.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.818

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 3-10026743-GCCAGATGGTA-G is Benign according to our data. Variant chr3-10026743-GCCAGATGGTA-G is described in ClinVar as [Benign]. Clinvar id is 1296735.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCD2	NM_001018115.3	c.-34+271_-34+280delCCAGATGGTA		intron_variant		ENST00000675286.1	NP_001018125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCD2	ENST00000675286.1	c.-34+271_-34+280delCCAGATGGTA		intron_variant			NM_001018115.3	ENSP00000502379.1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29730 AN: 151996 Hom.: 3366 Cov.: 27

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0650

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.168

GnomAD4 exome AF: 0.136 AC: 3 AN: 22 Hom.: 1 AF XY: 0.0833 AC XY: 1 AN XY: 12

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.196 AC: 29751 AN: 152114 Hom.: 3368 Cov.: 27 AF XY: 0.190 AC XY: 14155 AN XY: 74374

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.0650

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.168

Alfa AF: 0.181 Hom.: 347

Bravo AF: 0.206

Asia WGS AF: 0.113 AC: 396 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs140738485; hg19: chr3-10068427; COSMIC: COSV55041882; COSMIC: COSV55041882;