rs2709591

Positions:

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

2

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]

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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
ASAP2NM_003887.3 linkuse as main transcriptc.1161-17T>C splice_polypyrimidine_tract_variant, intron_variant ENST00000281419.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ASAP2ENST00000281419.8 linkuse as main transcriptc.1161-17T>C splice_polypyrimidine_tract_variant, intron_variant 1 NM_003887.3 P3O43150-1
ASAP2ENST00000315273.4 linkuse as main transcriptc.1161-17T>C splice_polypyrimidine_tract_variant, intron_variant 1 A1O43150-2
ASAP2ENST00000641030.1 linkuse as main transcriptc.700-17T>C splice_polypyrimidine_tract_variant, intron_variant
ASAP2ENST00000471687.1 linkuse as main transcriptn.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
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.:
53
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.:
32
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.

Other links and lift over

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