rs3801850

Variant names:

• chr7-26780958-T-C
• rs3801850
• NM_003930.5:c.308-40994A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.87).
• 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 rank	MANE	Protein	UniProt
SKAP2	NM_003930.5	c.308-40994A>G		intron_variant	Intron 4 of 12	ENST00000345317.7	NP_003921.2
SKAP2	NM_001303468.2	c.-209-40994A>G		intron_variant	Intron 4 of 12		NP_001290397.1
SKAP2	XM_017012771.3	c.308-40994A>G		intron_variant	Intron 4 of 12		XP_016868260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKAP2	ENST00000345317.7	c.308-40994A>G		intron_variant	Intron 4 of 12	1	NM_003930.5	ENSP00000005587.2

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

African (AFR) AF: 0.186 AC: 7736 AN: 41524

American (AMR) AF: 0.221 AC: 3370 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 877 AN: 3468

East Asian (EAS) AF: 0.0951 AC: 493 AN: 5182

South Asian (SAS) AF: 0.220 AC: 1061 AN: 4818

European-Finnish (FIN) AF: 0.193 AC: 2043 AN: 10604

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16034 AN: 67958

Other (OTH) AF: 0.208 AC: 438 AN: 2110

Alfa AF: 0.222 Hom.: 1787

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
PhyloP100		0.095
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: rs3801850; hg19: chr7-26820577;