rs7804356

Variant names:

• chr7-26852046-T-C
• rs7804356
• NM_003930.5:c.199+2091A>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.199+2091A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,030 control chromosomes in the GnomAD database, including 3,585 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 (3585 hom., cov: 31)
• Consequence: SKAP2 NM_003930.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101
• Publications: 84 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003930.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKAP2	NM_003930.5	MANE Select	c.199+2091A>G		intron	N/A	NP_003921.2
	SKAP2	NM_001303468.2		c.-318+2091A>G		intron	N/A	NP_001290397.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKAP2	ENST00000345317.7	TSL:1 MANE Select	c.199+2091A>G		intron	N/A	ENSP00000005587.2
	SKAP2	ENST00000432747.1	TSL:4	c.154+2091A>G		intron	N/A	ENSP00000408163.1
	SKAP2	ENST00000468712.5	TSL:2	n.360+2091A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32559 AN: 151912 Hom.: 3587 Cov.: 31

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.0960

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.214 AC: 32568 AN: 152030 Hom.: 3585 Cov.: 31 AF XY: 0.212 AC XY: 15778 AN XY: 74334

African (AFR) AF: 0.188 AC: 7784 AN: 41466

American (AMR) AF: 0.224 AC: 3426 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 928 AN: 3468

East Asian (EAS) AF: 0.0963 AC: 498 AN: 5174

South Asian (SAS) AF: 0.221 AC: 1067 AN: 4830

European-Finnish (FIN) AF: 0.190 AC: 2008 AN: 10568

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

European-Non Finnish (NFE) AF: 0.236 AC: 16041 AN: 67942

Other (OTH) AF: 0.209 AC: 441 AN: 2108

Alfa AF: 0.228 Hom.: 14070

Bravo AF: 0.216

Asia WGS AF: 0.156 AC: 544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.8
DANN	Benign	0.77
PhyloP100		0.10
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: rs7804356; hg19: chr7-26891665;