chr2-9374851-C-T
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_003887.3(ASAP2):c.1653C>T(p.Cys551=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000948 in 1,613,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00025 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000079 ( 0 hom. )
Consequence
ASAP2
NM_003887.3 synonymous
NM_003887.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.616
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 Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
Variant 2-9374851-C-T is Benign according to our data. Variant chr2-9374851-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 725859.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.616 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ASAP2 | NM_003887.3 | c.1653C>T | p.Cys551= | synonymous_variant | 17/28 | ENST00000281419.8 | NP_003878.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ASAP2 | ENST00000281419.8 | c.1653C>T | p.Cys551= | synonymous_variant | 17/28 | 1 | NM_003887.3 | ENSP00000281419 | P3 | |
ASAP2 | ENST00000315273.4 | c.1653C>T | p.Cys551= | synonymous_variant | 17/27 | 1 | ENSP00000316404 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000250 AC: 38AN: 152060Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000191 AC: 48AN: 251366Hom.: 0 AF XY: 0.000213 AC XY: 29AN XY: 135862
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GnomAD4 exome AF: 0.0000787 AC: 115AN: 1461796Hom.: 0 Cov.: 34 AF XY: 0.000103 AC XY: 75AN XY: 727214
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GnomAD4 genome AF: 0.000250 AC: 38AN: 152178Hom.: 0 Cov.: 31 AF XY: 0.000269 AC XY: 20AN XY: 74384
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 16, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at