chr2-9356162-T-C

Position:

• chr2-9356162-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003887.3(ASAP2):​c.1161-17T>C variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.998

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ASAP2	NM_003887.3	c.1161-17T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000281419.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASAP2	ENST00000281419.8	c.1161-17T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_003887.3	P3
ASAP2	ENST00000315273.4	c.1161-17T>C		splice_polypyrimidine_tract_variant, intron_variant		1		A1
ASAP2	ENST00000641030.1	c.700-17T>C		splice_polypyrimidine_tract_variant, intron_variant
ASAP2	ENST00000471687.1	n.487-17T>C		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes AF: 0.550 AC: 138197 AN: 251370 Hom.: 40818 AF XY: 0.550 AC XY: 74696 AN XY: 135846

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 SAS exome AF: 0.543

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

Gnomad4 AFR exome AF: 0.904

Gnomad4 AMR exome AF: 0.494

Gnomad4 ASJ exome AF: 0.636

Gnomad4 EAS exome AF: 0.157

Gnomad4 SAS exome AF: 0.542

Gnomad4 FIN exome AF: 0.528

Gnomad4 NFE exome AF: 0.584

Gnomad4 OTH exome AF: 0.585

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

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.641

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.630

Alfa AF: 0.597 Hom.: 38264

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2709591; hg19: chr2-9496291; COSMIC: COSV55638275;