3-10094466-C-T

Variant names:

• chr3-10094466-C-T
• rs7610821
• NM_001018115.3:c.3963+103C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001018115.3(FANCD2):​c.3963+103C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 949,642 control chromosomes in the GnomAD database, including 19,273 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (5960 hom., cov: 32)
  • Exomes 𝑓: 0.17 (13313 hom.)
• Consequence: FANCD2 NM_001018115.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0590
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-10094466-C-T is Benign according to our data. Variant chr3-10094466-C-T is described in ClinVar as Benign. ClinVar VariationId is 1235228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCD2	NM_001018115.3	c.3963+103C>T		intron_variant	Intron 40 of 43	ENST00000675286.1	NP_001018125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCD2	ENST00000675286.1	c.3963+103C>T		intron_variant	Intron 40 of 43		NM_001018115.3	ENSP00000502379.1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36746 AN: 151852 Hom.: 5953 Cov.: 32

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0905

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.171 AC: 136213 AN: 797672 Hom.: 13313 AF XY: 0.171 AC XY: 72467 AN XY: 422938

African (AFR) AF: 0.464 AC: 9641 AN: 20768

American (AMR) AF: 0.186 AC: 8065 AN: 43468

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 3417 AN: 21950

East Asian (EAS) AF: 0.0753 AC: 2749 AN: 36518

South Asian (SAS) AF: 0.210 AC: 15266 AN: 72660

European-Finnish (FIN) AF: 0.123 AC: 5447 AN: 44424

Middle Eastern (MID) AF: 0.162 AC: 706 AN: 4370

European-Non Finnish (NFE) AF: 0.163 AC: 84021 AN: 515248

Other (OTH) AF: 0.180 AC: 6901 AN: 38266

GnomAD4 genome AF: 0.242 AC: 36778 AN: 151970 Hom.: 5960 Cov.: 32 AF XY: 0.236 AC XY: 17559 AN XY: 74278

African (AFR) AF: 0.464 AC: 19195 AN: 41388

American (AMR) AF: 0.173 AC: 2646 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 521 AN: 3470

East Asian (EAS) AF: 0.0903 AC: 466 AN: 5160

South Asian (SAS) AF: 0.202 AC: 973 AN: 4814

European-Finnish (FIN) AF: 0.116 AC: 1231 AN: 10574

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11029 AN: 67986

Other (OTH) AF: 0.205 AC: 433 AN: 2112

Alfa AF: 0.0988 Hom.: 178

Bravo AF: 0.259

Asia WGS AF: 0.144 AC: 503 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 11, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.8
DANN	Benign	0.48
PhyloP100		-0.059
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7610821; hg19: chr3-10136150;