rs2709591

Variant names:

• chr2-9356162-T-C
• rs2709591
• NM_003887.3:c.1161-17T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003887.3(ASAP2):​c.1161-17T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 1,613,672 control chromosomes in the GnomAD database, including 281,056 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.65 (33982 hom., cov: 32)
  • Exomes 𝑓: 0.57 (247074 hom.)
• Consequence: ASAP2 NM_003887.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.998
• Publications: 19 publications found

Genes affected

ASAP2 (HGNC:2721): (ArfGAP with SH3 domain, ankyrin repeat and PH domain 2) This gene encodes a multidomain protein containing an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology (PH) domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal Src homology 3 (SH3) domain. The protein localizes in the Golgi apparatus and at the plasma membrane, where it colocalizes with protein tyrosine kinase 2-beta (PYK2). The encoded protein forms a stable complex with PYK2 in vivo. This interaction appears to be mediated by binding of its SH3 domain to the C-terminal proline-rich domain of PYK2. The encoded protein is tyrosine phosphorylated by activated PYK2. It has catalytic activity for class I and II ArfGAPs in vitro, and can bind the class III Arf ARF6 without immediate GAP activity. The encoded protein is believed to function as an ARF GAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. In addition, it functions as a substrate and downstream target for PYK2 and SRC, a pathway that may be involved in the regulation of vesicular transport. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASAP2	NM_003887.3	c.1161-17T>C		intron_variant	Intron 13 of 27	ENST00000281419.8	NP_003878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASAP2	ENST00000281419.8	c.1161-17T>C		intron_variant	Intron 13 of 27	1	NM_003887.3	ENSP00000281419.3
ASAP2	ENST00000315273.4	c.1161-17T>C		intron_variant	Intron 13 of 26	1		ENSP00000316404.4
ASAP2	ENST00000641030.1	c.699-17T>C		intron_variant	Intron 9 of 10			ENSP00000493293.1
ASAP2	ENST00000471687.1	n.487-17T>C		intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98191 AN: 151932 Hom.: 33929 Cov.: 32

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.633

GnomAD2 exomes AF: 0.550 AC: 138197 AN: 251370 AF XY: 0.550

Gnomad AFR exome AF: 0.893

Gnomad AMR exome AF: 0.481

Gnomad ASJ exome AF: 0.636

Gnomad EAS exome AF: 0.158

Gnomad FIN exome AF: 0.525

Gnomad NFE exome AF: 0.583

Gnomad OTH exome AF: 0.573

GnomAD4 exome AF: 0.574 AC: 838279 AN: 1461622 Hom.: 247074 Cov.: 53 AF XY: 0.573 AC XY: 416692 AN XY: 727106

African (AFR) AF: 0.904 AC: 30253 AN: 33474

American (AMR) AF: 0.494 AC: 22081 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 16621 AN: 26136

East Asian (EAS) AF: 0.157 AC: 6251 AN: 39696

South Asian (SAS) AF: 0.542 AC: 46765 AN: 86250

European-Finnish (FIN) AF: 0.528 AC: 28203 AN: 53420

Middle Eastern (MID) AF: 0.655 AC: 3779 AN: 5768

European-Non Finnish (NFE) AF: 0.584 AC: 649014 AN: 1111766

Other (OTH) AF: 0.585 AC: 35312 AN: 60390

GnomAD4 genome AF: 0.647 AC: 98302 AN: 152050 Hom.: 33982 Cov.: 32 AF XY: 0.639 AC XY: 47471 AN XY: 74326

African (AFR) AF: 0.889 AC: 36869 AN: 41484

American (AMR) AF: 0.570 AC: 8705 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2222 AN: 3466

East Asian (EAS) AF: 0.164 AC: 846 AN: 5172

South Asian (SAS) AF: 0.538 AC: 2591 AN: 4818

European-Finnish (FIN) AF: 0.510 AC: 5382 AN: 10554

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39528 AN: 67958

Other (OTH) AF: 0.630 AC: 1331 AN: 2112

Alfa AF: 0.605 Hom.: 49483

Bravo AF: 0.658

Asia WGS AF: 0.398 AC: 1382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.33
PhyloP100		1.0
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: rs2709591; hg19: chr2-9496291; COSMIC: COSV55638275;