rs17291131

chr7-26690121-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003930.5(SKAP2):c.874+164C>T variant causes a intron change. The variant allele was found at a frequency of 0.0881 in 152,246 control chromosomes in the GnomAD database, including 762 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 0.088 (762 hom., cov: 32)
• Consequence: SKAP2 NM_003930.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.51

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SKAP2	NM_003930.5	c.874+164C>T		intron_variant		ENST00000345317.7
SKAP2	NM_001303468.2	c.358+164C>T		intron_variant
SKAP2	XM_017012771.3	c.874+164C>T		intron_variant
SKAP2	XM_047421010.1	c.358+164C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SKAP2	ENST00000345317.7	c.874+164C>T		intron_variant		1	NM_003930.5	P1

Frequencies

GnomAD3 genomes AF: 0.0882 AC: 13416 AN: 152128 Hom.: 764 Cov.: 32

Gnomad AFR AF: 0.0286

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.0677

Gnomad ASJ AF: 0.0717

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0628

Gnomad FIN AF: 0.0907

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.0826

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0881 AC: 13417 AN: 152246 Hom.: 762 Cov.: 32 AF XY: 0.0848 AC XY: 6314 AN XY: 74432

Gnomad4 AFR AF: 0.0286

Gnomad4 AMR AF: 0.0674

Gnomad4 ASJ AF: 0.0717

Gnomad4 EAS AF: 0.00386

Gnomad4 SAS AF: 0.0635

Gnomad4 FIN AF: 0.0907

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.0822

Alfa AF: 0.123 Hom.: 1918

Bravo AF: 0.0822

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
Cadd	Benign	22
Dann	Benign	0.82

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: rs17291131; hg19: chr7-26729740;