rs7647987

Variant names:

• chr3-10099012-A-G
• rs7647987
• ENST00000287647.7:c.*62A>G

Variant summary

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

The NM_033084.6(FANCD2):​c.*62A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,612,436 control chromosomes in the GnomAD database, including 29,915 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (5952 hom., cov: 32)
  • Exomes 𝑓: 0.17 (23963 hom.)
• Consequence: FANCD2 NM_033084.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.424
• Publications: 32 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=-0.87).
• BP6: Variant 3-10099012-A-G is Benign according to our data. Variant chr3-10099012-A-G is described in ClinVar as Benign. ClinVar VariationId is 342383.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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033084.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCD2	NM_001018115.3	MANE Select	c.4281+197A>G		intron	N/A	NP_001018125.1	Q9BXW9-2
	FANCD2	NM_033084.6		c.*62A>G		3_prime_UTR	Exon 43 of 43	NP_149075.2
	FANCD2	NM_001374254.1		c.*62A>G		3_prime_UTR	Exon 42 of 42	NP_001361183.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCD2	ENST00000287647.7	TSL:1	c.*62A>G		3_prime_UTR	Exon 43 of 43	ENSP00000287647.3	Q9BXW9-1
	FANCD2	ENST00000675286.1	MANE Select	c.4281+197A>G		intron	N/A	ENSP00000502379.1	Q9BXW9-2
	FANCD2	ENST00000419585.5	TSL:1	c.4281+197A>G		intron	N/A	ENSP00000398754.1	Q9BXW9-2

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36737 AN: 151828 Hom.: 5944 Cov.: 32

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0899

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.207

GnomAD4 exome AF: 0.173 AC: 252548 AN: 1460492 Hom.: 23963 Cov.: 33 AF XY: 0.173 AC XY: 125534 AN XY: 726614

African (AFR) AF: 0.474 AC: 15854 AN: 33452

American (AMR) AF: 0.186 AC: 8282 AN: 44604

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 4100 AN: 26122

East Asian (EAS) AF: 0.0759 AC: 3013 AN: 39692

South Asian (SAS) AF: 0.210 AC: 18063 AN: 86118

European-Finnish (FIN) AF: 0.123 AC: 6515 AN: 52778

Middle Eastern (MID) AF: 0.172 AC: 990 AN: 5752

European-Non Finnish (NFE) AF: 0.166 AC: 184772 AN: 1111606

Other (OTH) AF: 0.182 AC: 10959 AN: 60368

GnomAD4 genome AF: 0.242 AC: 36774 AN: 151944 Hom.: 5952 Cov.: 32 AF XY: 0.236 AC XY: 17561 AN XY: 74260

African (AFR) AF: 0.463 AC: 19184 AN: 41424

American (AMR) AF: 0.174 AC: 2650 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 523 AN: 3470

East Asian (EAS) AF: 0.0898 AC: 463 AN: 5158

South Asian (SAS) AF: 0.202 AC: 971 AN: 4814

European-Finnish (FIN) AF: 0.116 AC: 1228 AN: 10544

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

European-Non Finnish (NFE) AF: 0.162 AC: 11036 AN: 67948

Other (OTH) AF: 0.206 AC: 436 AN: 2112

Alfa AF: 0.197 Hom.: 7852

Bravo AF: 0.258

Asia WGS AF: 0.146 AC: 511 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Fanconi anemia complementation group D2 (1)
-	-	1	Hereditary breast ovarian cancer syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.65
DANN	Benign	0.57
PhyloP100		-0.42
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: rs7647987; hg19: chr3-10140696; COSMIC: COSV55047463;