rs17291131

Variant names:

• chr7-26690121-G-A
• rs17291131
• NM_003930.5:c.874+164C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SKAP2	NM_003930.5	c.874+164C>T		intron_variant	Intron 10 of 12	ENST00000345317.7	NP_003921.2
SKAP2	NM_001303468.2	c.358+164C>T		intron_variant	Intron 10 of 12		NP_001290397.1
SKAP2	XM_017012771.3	c.874+164C>T		intron_variant	Intron 10 of 12		XP_016868260.1
SKAP2	XM_047421010.1	c.358+164C>T		intron_variant	Intron 7 of 9		XP_047276966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKAP2	ENST00000345317.7	c.874+164C>T		intron_variant	Intron 10 of 12	1	NM_003930.5	ENSP00000005587.2
SKAP2	ENST00000489977.5	n.*186C>T		downstream_gene_variant		5

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

African (AFR) AF: 0.0286 AC: 1190 AN: 41560

American (AMR) AF: 0.0674 AC: 1031 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0717 AC: 249 AN: 3472

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5182

South Asian (SAS) AF: 0.0635 AC: 306 AN: 4822

European-Finnish (FIN) AF: 0.0907 AC: 962 AN: 10602

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9443 AN: 67998

Other (OTH) AF: 0.0822 AC: 174 AN: 2116

Alfa AF: 0.119 Hom.: 2713

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
PhyloP100		5.5
Mutation Taster		=92/8	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17291131; hg19: chr7-26729740;