rs4719882

Positions:

• chr7-26842633-A-G

Variant summary

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

The NM_003930.5(SKAP2):​c.307+1397T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 151,742 control chromosomes in the GnomAD database, including 3,508 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 (3508 hom., cov: 32)
• Consequence: SKAP2 NM_003930.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537

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]

LOC124901606 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• 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.307+1397T>C		intron_variant		ENST00000345317.7	NP_003921.2
LOC124901606	XR_007060265.1	n.201-14831A>G		intron_variant, non_coding_transcript_variant
SKAP2	NM_001303468.2	c.-210+1397T>C		intron_variant			NP_001290397.1
SKAP2	XM_017012771.3	c.307+1397T>C		intron_variant			XP_016868260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SKAP2	ENST00000345317.7	c.307+1397T>C		intron_variant		1	NM_003930.5	ENSP00000005587	P1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32218 AN: 151622 Hom.: 3509 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.0959

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.208

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.212 AC: 32222 AN: 151742 Hom.: 3508 Cov.: 32 AF XY: 0.210 AC XY: 15600 AN XY: 74138

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.0961

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.207

Alfa AF: 0.210 Hom.: 434

Bravo AF: 0.213

Asia WGS AF: 0.152 AC: 522 AN: 3430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.12
DANN	Benign	0.60

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: rs4719882; hg19: chr7-26882252;