rs774265

Positions:

• chr7-26919298-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000432747.1(SKAP2):​c.-113-25325C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,086 control chromosomes in the GnomAD database, including 2,312 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 0.16 (2312 hom., cov: 32)
• Consequence: SKAP2 ENST00000432747.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.216

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SKAP2	ENST00000432747.1	c.-113-25325C>T		intron_variant		4		ENSP00000408163

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24031 AN: 151968 Hom.: 2312 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.00597

Gnomad SAS AF: 0.0706

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.158 AC: 24040 AN: 152086 Hom.: 2312 Cov.: 32 AF XY: 0.154 AC XY: 11470 AN XY: 74348

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.00598

Gnomad4 SAS AF: 0.0705

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.164

Alfa AF: 0.139 Hom.: 1848

Bravo AF: 0.165

Asia WGS AF: 0.0470 AC: 163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs774265; hg19: chr7-26958917;