rs56334136

Positions:

• chr3-10063977-CT-C
• chr3-10063977-CTT-C

Variant summary

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

The NM_001018115.3(FANCD2):​c.1947+69del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 32)
  • Exomes 𝑓: 0.023 (14 hom.)
  • Failed GnomAD Quality Control
• Consequence: FANCD2 NM_001018115.3 intron
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.373

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 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCD2	NM_001018115.3	c.1947+69del		intron_variant		ENST00000675286.1	NP_001018125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCD2	ENST00000675286.1	c.1947+69del		intron_variant			NM_001018115.3	ENSP00000502379	P2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 183 AN: 139940 Hom.: 1 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.000580

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000214

Gnomad ASJ AF: 0.000307

Gnomad EAS AF: 0.000414

Gnomad SAS AF: 0.0217

Gnomad FIN AF: 0.000308

Gnomad MID AF: 0.00329

Gnomad NFE AF: 0.000860

Gnomad OTH AF: 0.00159

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0226 AC: 28994 AN: 1280124 Hom.: 14 AF XY: 0.0254 AC XY: 16116 AN XY: 634840

Gnomad4 AFR exome AF: 0.0168

Gnomad4 AMR exome AF: 0.0113

Gnomad4 ASJ exome AF: 0.00907

Gnomad4 EAS exome AF: 0.0122

Gnomad4 SAS exome AF: 0.0246

Gnomad4 FIN exome AF: 0.0361

Gnomad4 NFE exome AF: 0.0234

Gnomad4 OTH exome AF: 0.0192

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00129 AC: 181 AN: 140058 Hom.: 1 Cov.: 32 AF XY: 0.00174 AC XY: 118 AN XY: 67958

Gnomad4 AFR AF: 0.000578

Gnomad4 AMR AF: 0.000214

Gnomad4 ASJ AF: 0.000307

Gnomad4 EAS AF: 0.000415

Gnomad4 SAS AF: 0.0212

Gnomad4 FIN AF: 0.000308

Gnomad4 NFE AF: 0.000860

Gnomad4 OTH AF: 0.00157

Alfa AF: 0.00274 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 12, 2015

- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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: rs797045572; hg19: chr3-10105661;