rs774265

Variant names:

• chr7-26919298-G-A
• rs774265
• ENST00000432747.1:c.-113-25325C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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 -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKAP2	ENST00000432747.1	c.-113-25325C>T		intron_variant	Intron 1 of 6	4		ENSP00000408163.1

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

African (AFR) AF: 0.255 AC: 10590 AN: 41484

American (AMR) AF: 0.115 AC: 1752 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 463 AN: 3464

East Asian (EAS) AF: 0.00598 AC: 31 AN: 5182

South Asian (SAS) AF: 0.0705 AC: 340 AN: 4824

European-Finnish (FIN) AF: 0.109 AC: 1153 AN: 10598

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9301 AN: 67972

Other (OTH) AF: 0.164 AC: 346 AN: 2108

Alfa AF: 0.142 Hom.: 5171

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
PhyloP100		0.22

Splicing

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

Other links and lift over

dbSNP: rs774265; hg19: chr7-26958917;