Variant chr7-26738871-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_003930.5(SKAP2):c.393C>T(p.Ser131=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00349 in 1,590,752 control chromosomes in the GnomAD database, including 151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.019 ( 86 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 65 hom. )

Consequence

SKAP2
NM_003930.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.35

Variant links:

Genes affected

SKAP2 (HGNC:15687): (src kinase associated phosphoprotein 2) The protein encoded by this gene shares homology with Src kinase-associated phosphoprotein 1, and is a substrate of Src family kinases. It is an adaptor protein that is thought to play an essential role in the Src signaling pathway, and in regulating proper activation of the immune system. This protein contains an amino terminal coiled-coil domain for self-dimerization, a plecskstrin homology (PH) domain required for interactions with lipids at the membrane, and a Src homology (SH3) domain at the carboxy terminus. Some reports indicate that this protein inhibits actin polymerization through interactions with actin assembly factors, and might negatively regulate the invasiveness of tumors by modulating actin assembly. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2015]

SKAP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 7-26738871-G-A is Benign according to our data. Variant chr7-26738871-G-A is described in ClinVar as [Benign]. Clinvar id is 776211.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.35 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SKAP2	NM_003930.5 linkuse as main transcript	c.393C>T	p.Ser131=	synonymous_variant	6/13	ENST00000345317.7
SKAP2	XM_017012771.3 linkuse as main transcript	c.393C>T	p.Ser131=	synonymous_variant	6/13
SKAP2	NM_001303468.2 linkuse as main transcript	c.-124C>T		5_prime_UTR_variant	6/13
SKAP2	XM_047421010.1 linkuse as main transcript	c.-124C>T		5_prime_UTR_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SKAP2	ENST00000345317.7 linkuse as main transcript	c.393C>T	p.Ser131=	synonymous_variant	6/13	1	NM_003930.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0186

AC:

2824

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0644

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00734

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.00525

AC:

1316

AN:

250594

Hom.:

AF XY:

0.00385

AC XY:

522

AN XY:

135442

show subpopulations

Gnomad AFR exome

AF:

0.0656

Gnomad AMR exome

AF:

0.00617

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00262

GnomAD4 exome

AF:

0.00189

AC:

2724

AN:

1438558

Hom.:

Cov.:

AF XY:

0.00163

AC XY:

1168

AN XY:

717310

show subpopulations

Gnomad4 AFR exome

AF:

0.0581

Gnomad4 AMR exome

AF:

0.00723

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000700

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000204

Gnomad4 OTH exome

AF:

0.00420

GnomAD4 genome

AF:

0.0186

AC:

2825

AN:

152194

Hom.:

Cov.:

AF XY:

0.0174

AC XY:

1298

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0642

Gnomad4 AMR

AF:

0.00733

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00510

Hom.:

Bravo

AF:

0.0215

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over