7-26852046-T-C

Position:

• chr7-26852046-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SKAP2	NM_003930.5	c.199+2091A>G		intron_variant		ENST00000345317.7
LOC124901606	XR_007060265.1	n.201-5418T>C		intron_variant, non_coding_transcript_variant
SKAP2	NM_001303468.2	c.-318+2091A>G		intron_variant
SKAP2	XM_017012771.3	c.199+2091A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SKAP2	ENST00000345317.7	c.199+2091A>G		intron_variant		1	NM_003930.5	P1

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

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.0963

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.209

Alfa AF: 0.231 Hom.: 6345

Bravo AF: 0.216

Asia WGS AF: 0.156 AC: 544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.8
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs7804356; hg19: chr7-26891665;