rs2159116

Variant names:

• chr16-89765102-C-A
• rs2159116
• NM_000135.4:c.2602-36G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-89765102-C-A
• chr16-89765102-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_000135.4(FANCA):​c.2602-36G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,610,760 control chromosomes in the GnomAD database, including 22,894 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1477 hom., cov: 33)
  • Exomes 𝑓: 0.16 (21417 hom.)
• Consequence: FANCA NM_000135.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.70
• Publications: 23 publications found

Genes affected

FANCA (HGNC:3582): (FA complementation group A) 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 A. Alternative splicing results in multiple transcript variants encoding different isoforms. Mutations in this gene are the most common cause of Fanconi anemia. [provided by RefSeq, Jul 2008]

FANCA Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, G2P
• 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 16-89765102-C-A is Benign according to our data. Variant chr16-89765102-C-A is described in ClinVar as Benign. ClinVar VariationId is 255248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000135.4. 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
	FANCA	NM_000135.4	MANE Select	c.2602-36G>T		intron	N/A	NP_000126.2
	FANCA	NM_001286167.3		c.2602-36G>T		intron	N/A	NP_001273096.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCA	ENST00000389301.8	TSL:1 MANE Select	c.2602-36G>T		intron	N/A	ENSP00000373952.3
	FANCA	ENST00000564475.6	TSL:2	c.2602-36G>T		intron	N/A	ENSP00000454977.2
	FANCA	ENST00000568369.6	TSL:2	c.2602-36G>T		intron	N/A	ENSP00000456829.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18621 AN: 152126 Hom.: 1477 Cov.: 33

Gnomad AFR AF: 0.0382

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.00443

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.151

GnomAD2 exomes AF: 0.145 AC: 36116 AN: 248354 AF XY: 0.153

Gnomad AFR exome AF: 0.0354

Gnomad AMR exome AF: 0.0997

Gnomad ASJ exome AF: 0.183

Gnomad EAS exome AF: 0.00334

Gnomad FIN exome AF: 0.143

Gnomad NFE exome AF: 0.184

Gnomad OTH exome AF: 0.162

GnomAD4 exome AF: 0.165 AC: 240568 AN: 1458516 Hom.: 21417 Cov.: 32 AF XY: 0.167 AC XY: 120937 AN XY: 725560

African (AFR) AF: 0.0358 AC: 1195 AN: 33414

American (AMR) AF: 0.104 AC: 4614 AN: 44498

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 4795 AN: 26090

East Asian (EAS) AF: 0.00182 AC: 72 AN: 39636

South Asian (SAS) AF: 0.187 AC: 16074 AN: 85876

European-Finnish (FIN) AF: 0.146 AC: 7752 AN: 53132

Middle Eastern (MID) AF: 0.276 AC: 1591 AN: 5766

European-Non Finnish (NFE) AF: 0.176 AC: 195043 AN: 1109876

Other (OTH) AF: 0.157 AC: 9432 AN: 60228

GnomAD4 genome AF: 0.122 AC: 18611 AN: 152244 Hom.: 1477 Cov.: 33 AF XY: 0.120 AC XY: 8952 AN XY: 74454

African (AFR) AF: 0.0380 AC: 1580 AN: 41556

American (AMR) AF: 0.121 AC: 1854 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 603 AN: 3468

East Asian (EAS) AF: 0.00444 AC: 23 AN: 5184

South Asian (SAS) AF: 0.171 AC: 826 AN: 4820

European-Finnish (FIN) AF: 0.135 AC: 1427 AN: 10604

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11742 AN: 67994

Other (OTH) AF: 0.150 AC: 317 AN: 2116

Alfa AF: 0.107 Hom.: 491

Bravo AF: 0.118

Asia WGS AF: 0.0920 AC: 320 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Fanconi anemia complementation group A (3)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.34
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2159116; hg19: chr16-89831510; COSMIC: COSV59796461; COSMIC: COSV59796461;