rs9809061

Variant names:

• chr3-10043446-C-G
• rs9809061
• NM_001018115.3:c.990-38C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-10043446-C-G
• chr3-10043446-C-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.990-38C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,510,920 control chromosomes in the GnomAD database, including 25,916 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (5025 hom., cov: 32)
  • Exomes 𝑓: 0.17 (20891 hom.)
• Consequence: FANCD2 NM_001018115.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.925
• Publications: 8 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]

FANCD2 Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group D2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-10043446-C-G is Benign according to our data. Variant chr3-10043446-C-G is described in ClinVar as Benign. ClinVar VariationId is 257088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001018115.3. 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.990-38C>G		intron	N/A	NP_001018125.1	Q9BXW9-2
	FANCD2	NM_033084.6		c.990-38C>G		intron	N/A	NP_149075.2
	FANCD2	NM_001374254.1		c.990-38C>G		intron	N/A	NP_001361183.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCD2	ENST00000675286.1	MANE Select	c.990-38C>G		intron	N/A	ENSP00000502379.1	Q9BXW9-2
	FANCD2	ENST00000287647.7	TSL:1	c.990-38C>G		intron	N/A	ENSP00000287647.3	Q9BXW9-1
	FANCD2	ENST00000419585.5	TSL:1	c.990-38C>G		intron	N/A	ENSP00000398754.1	Q9BXW9-2

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34328 AN: 151836 Hom.: 5019 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0654

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.194

GnomAD2 exomes AF: 0.167 AC: 41368 AN: 247316 AF XY: 0.165

Gnomad AFR exome AF: 0.432

Gnomad AMR exome AF: 0.157

Gnomad ASJ exome AF: 0.158

Gnomad EAS exome AF: 0.0653

Gnomad FIN exome AF: 0.120

Gnomad NFE exome AF: 0.158

Gnomad OTH exome AF: 0.159

GnomAD4 exome AF: 0.168 AC: 228455 AN: 1358966 Hom.: 20891 Cov.: 21 AF XY: 0.168 AC XY: 114340 AN XY: 682076

African (AFR) AF: 0.429 AC: 13470 AN: 31410

American (AMR) AF: 0.162 AC: 7186 AN: 44464

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 4003 AN: 25534

East Asian (EAS) AF: 0.0566 AC: 2218 AN: 39198

South Asian (SAS) AF: 0.180 AC: 15156 AN: 84110

European-Finnish (FIN) AF: 0.124 AC: 6619 AN: 53342

Middle Eastern (MID) AF: 0.169 AC: 937 AN: 5556

European-Non Finnish (NFE) AF: 0.166 AC: 168987 AN: 1018370

Other (OTH) AF: 0.173 AC: 9879 AN: 56982

GnomAD4 genome AF: 0.226 AC: 34364 AN: 151954 Hom.: 5025 Cov.: 32 AF XY: 0.220 AC XY: 16368 AN XY: 74270

African (AFR) AF: 0.420 AC: 17391 AN: 41390

American (AMR) AF: 0.155 AC: 2373 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 523 AN: 3466

East Asian (EAS) AF: 0.0654 AC: 338 AN: 5172

South Asian (SAS) AF: 0.163 AC: 785 AN: 4824

European-Finnish (FIN) AF: 0.117 AC: 1235 AN: 10554

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.162 AC: 11025 AN: 67970

Other (OTH) AF: 0.194 AC: 410 AN: 2112

Alfa AF: 0.113 Hom.: 224

Bravo AF: 0.240

Asia WGS AF: 0.125 AC: 438 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.8
DANN	Benign	0.53
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs9809061; hg19: chr3-10085130;