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GeneBe

7-26738871-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_003930.5(SKAP2):c.393C>T(p.Ser131=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00349 in 1,590,752 control chromosomes in the GnomAD database, including 151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.019 ( 86 hom., cov: 32)
Exomes 𝑓: 0.0019 ( 65 hom. )

Consequence

SKAP2
NM_003930.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.35
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-26738871-G-A is Benign according to our data. Variant chr7-26738871-G-A is described in ClinVar as [Benign]. Clinvar id is 776211.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.35 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0622 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SKAP2NM_003930.5 linkuse as main transcriptc.393C>T p.Ser131= synonymous_variant 6/13 ENST00000345317.7
SKAP2XM_017012771.3 linkuse as main transcriptc.393C>T p.Ser131= synonymous_variant 6/13
SKAP2NM_001303468.2 linkuse as main transcriptc.-124C>T 5_prime_UTR_variant 6/13
SKAP2XM_047421010.1 linkuse as main transcriptc.-124C>T 5_prime_UTR_variant 3/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SKAP2ENST00000345317.7 linkuse as main transcriptc.393C>T p.Ser131= synonymous_variant 6/131 NM_003930.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0186
AC:
2824
AN:
152076
Hom.:
87
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0644
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00734
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000250
Gnomad OTH
AF:
0.0139
GnomAD3 exomes
AF:
0.00525
AC:
1316
AN:
250594
Hom.:
44
AF XY:
0.00385
AC XY:
522
AN XY:
135442
show subpopulations
Gnomad AFR exome
AF:
0.0656
Gnomad AMR exome
AF:
0.00617
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000185
Gnomad OTH exome
AF:
0.00262
GnomAD4 exome
AF:
0.00189
AC:
2724
AN:
1438558
Hom.:
65
Cov.:
27
AF XY:
0.00163
AC XY:
1168
AN XY:
717310
show subpopulations
Gnomad4 AFR exome
AF:
0.0581
Gnomad4 AMR exome
AF:
0.00723
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000700
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000204
Gnomad4 OTH exome
AF:
0.00420
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0186
AC:
2825
AN:
152194
Hom.:
86
Cov.:
32
AF XY:
0.0174
AC XY:
1298
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.0642
Gnomad4 AMR
AF:
0.00733
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000250
Gnomad4 OTH
AF:
0.0137
Alfa
AF:
0.00510
Hom.:
7
Bravo
AF:
0.0215
Asia WGS
AF:
0.00260
AC:
9
AN:
3478
EpiCase
AF:
0.000327
EpiControl
AF:
0.000415

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 16, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.36
Cadd
Benign
12
Dann
Benign
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs34506751; hg19: chr7-26778490; API