Variant 2-9356162-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.998

Variant links:

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]

ASAP2 links:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.1161-17T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000281419.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
ASAP2	ENST00000281419.8 linkuse as main transcript	c.1161-17T>C	splice_polypyrimidine_tract_variant, intron_variant	1	NM_003887.3	P3	O43150-1
ASAP2	ENST00000315273.4 linkuse as main transcript	c.1161-17T>C	splice_polypyrimidine_tract_variant, intron_variant	1		A1	O43150-2
ASAP2	ENST00000641030.1 linkuse as main transcript	c.700-17T>C	splice_polypyrimidine_tract_variant, intron_variant
ASAP2	ENST00000471687.1 linkuse as main transcript	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.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.573

AC XY:

416692

AN XY:

727106

show subpopulations

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.:

AF XY:

0.639

AC XY:

47471

AN XY:

74326

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over