rs3801813

Variant names:

• chr7-26847450-T-C
• rs3801813
• NM_003930.5:c.200-3313A>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.200-3313A>G 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 151,650 control chromosomes in the GnomAD database, including 3,492 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 (3492 hom., cov: 31)
• Consequence: SKAP2 NM_003930.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71
• Publications: 10 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]

LOC124901606 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• 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.200-3313A>G		intron_variant	Intron 3 of 12	ENST00000345317.7	NP_003921.2
SKAP2	NM_001303468.2	c.-317-3313A>G		intron_variant	Intron 3 of 12		NP_001290397.1
SKAP2	XM_017012771.3	c.200-3313A>G		intron_variant	Intron 3 of 12		XP_016868260.1
LOC124901606	XR_007060265.1	n.201-10014T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKAP2	ENST00000345317.7	c.200-3313A>G		intron_variant	Intron 3 of 12	1	NM_003930.5	ENSP00000005587.2

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32180 AN: 151540 Hom.: 3494 Cov.: 31

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.0966

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.212 AC: 32180 AN: 151650 Hom.: 3492 Cov.: 31 AF XY: 0.210 AC XY: 15587 AN XY: 74054

African (AFR) AF: 0.181 AC: 7481 AN: 41296

American (AMR) AF: 0.222 AC: 3381 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 932 AN: 3468

East Asian (EAS) AF: 0.0968 AC: 500 AN: 5166

South Asian (SAS) AF: 0.213 AC: 1020 AN: 4782

European-Finnish (FIN) AF: 0.194 AC: 2034 AN: 10468

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16020 AN: 67906

Other (OTH) AF: 0.209 AC: 439 AN: 2102

Alfa AF: 0.113 Hom.: 176

Bravo AF: 0.213

Asia WGS AF: 0.152 AC: 529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Benign	0.48
PhyloP100		1.7
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: rs3801813; hg19: chr7-26887069;