7-26780958-T-C

Position:

• chr7-26780958-T-C

Variant summary

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

The NM_003930.5(SKAP2):​c.308-40994A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,136 control chromosomes in the GnomAD database, including 3,551 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 0.21 (3551 hom., cov: 32)
• Consequence: SKAP2 NM_003930.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SKAP2	NM_003930.5	c.308-40994A>G		intron_variant		ENST00000345317.7	NP_003921.2
SKAP2	NM_001303468.2	c.-209-40994A>G		intron_variant			NP_001290397.1
SKAP2	XM_017012771.3	c.308-40994A>G		intron_variant			XP_016868260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SKAP2	ENST00000345317.7	c.308-40994A>G		intron_variant		1	NM_003930.5	ENSP00000005587	P1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32427 AN: 152018 Hom.: 3553 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.0949

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.213 AC: 32427 AN: 152136 Hom.: 3551 Cov.: 32 AF XY: 0.211 AC XY: 15706 AN XY: 74378

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.0951

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.208

Alfa AF: 0.222 Hom.: 1501

Bravo AF: 0.214

Asia WGS AF: 0.154 AC: 538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.42

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: rs3801850; hg19: chr7-26820577;