rs17310268

Variant names:

• chr7-26690806-G-A
• rs17310268
• NM_003930.5:c.797-444C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003930.5(SKAP2):​c.797-444C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0813 in 152,220 control chromosomes in the GnomAD database, including 589 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 0.081 (589 hom., cov: 32)
• Consequence: SKAP2 NM_003930.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.217
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKAP2	NM_003930.5	c.797-444C>T		intron_variant	Intron 9 of 12	ENST00000345317.7	NP_003921.2
SKAP2	NM_001303468.2	c.281-444C>T		intron_variant	Intron 9 of 12		NP_001290397.1
SKAP2	XM_017012771.3	c.797-444C>T		intron_variant	Intron 9 of 12		XP_016868260.1
SKAP2	XM_047421010.1	c.281-444C>T		intron_variant	Intron 6 of 9		XP_047276966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKAP2	ENST00000345317.7	c.797-444C>T		intron_variant	Intron 9 of 12	1	NM_003930.5	ENSP00000005587.2
SKAP2	ENST00000489977.5	n.624-444C>T		intron_variant	Intron 6 of 6	5

Frequencies

GnomAD3 genomes AF: 0.0814 AC: 12379 AN: 152102 Hom.: 587 Cov.: 32

Gnomad AFR AF: 0.0328

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.0837

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.0931

Gnomad FIN AF: 0.0848

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.0813 AC: 12380 AN: 152220 Hom.: 589 Cov.: 32 AF XY: 0.0801 AC XY: 5965 AN XY: 74424

African (AFR) AF: 0.0328 AC: 1362 AN: 41550

American (AMR) AF: 0.0836 AC: 1279 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 594 AN: 3470

East Asian (EAS) AF: 0.0210 AC: 109 AN: 5184

South Asian (SAS) AF: 0.0938 AC: 453 AN: 4832

European-Finnish (FIN) AF: 0.0848 AC: 898 AN: 10584

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7258 AN: 67986

Other (OTH) AF: 0.0999 AC: 211 AN: 2112

Alfa AF: 0.0946 Hom.: 84

Bravo AF: 0.0782

Asia WGS AF: 0.0510 AC: 178 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.5
DANN	Benign	0.67
PhyloP100		-0.22
Mutation Taster		=100/0	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: rs17310268; hg19: chr7-26730425;