rs3801863

Variant names:

• chr7-26758893-G-T
• rs3801863
• NM_003930.5:c.308-18929C>A

Variant summary

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

The NM_003930.5(SKAP2):​c.308-18929C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0552 in 152,164 control chromosomes in the GnomAD database, including 410 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 0.055 (410 hom., cov: 33)
• Consequence: SKAP2 NM_003930.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKAP2	NM_003930.5	c.308-18929C>A		intron_variant	Intron 4 of 12	ENST00000345317.7	NP_003921.2
SKAP2	NM_001303468.2	c.-209-18929C>A		intron_variant	Intron 4 of 12		NP_001290397.1
SKAP2	XM_017012771.3	c.308-18929C>A		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.308-18929C>A		intron_variant	Intron 4 of 12	1	NM_003930.5	ENSP00000005587.2

Frequencies

GnomAD3 genomes AF: 0.0552 AC: 8388 AN: 152046 Hom.: 412 Cov.: 33

Gnomad AFR AF: 0.0451

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0568

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0487

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0422

Gnomad OTH AF: 0.0541

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

GnomAD4 genome AF: 0.0552 AC: 8400 AN: 152164 Hom.: 410 Cov.: 33 AF XY: 0.0576 AC XY: 4283 AN XY: 74400

African (AFR) AF: 0.0451 AC: 1871 AN: 41514

American (AMR) AF: 0.0568 AC: 870 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0233 AC: 81 AN: 3472

East Asian (EAS) AF: 0.281 AC: 1451 AN: 5166

South Asian (SAS) AF: 0.103 AC: 494 AN: 4816

European-Finnish (FIN) AF: 0.0487 AC: 515 AN: 10576

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0422 AC: 2872 AN: 67998

Other (OTH) AF: 0.0583 AC: 123 AN: 2110

Alfa AF: 0.0486 Hom.: 50

Bravo AF: 0.0547

Asia WGS AF: 0.187 AC: 649 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.2
DANN	Benign	0.76
PhyloP100		0.25
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: rs3801863; hg19: chr7-26798512;