20-36641316-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032214.4(SLA2):​c.20G>A​(p.Arg7Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R7I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLA2
NM_032214.4 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.19
Variant links:
Genes affected
SLA2 (HGNC:17329): (Src like adaptor 2) This gene encodes a member of the SLAP family of adapter proteins. The encoded protein may play an important receptor-proximal role in downregulating T and B cell-mediated responses and inhibits antigen receptor-induced calcium mobilization. This protein interacts with Cas-Br-M (murine) ecotropic retroviral transforming sequence c. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12389153).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLA2NM_032214.4 linkc.20G>A p.Arg7Lys missense_variant Exon 2 of 8 ENST00000262866.9 NP_115590.1 Q9H6Q3-1
SLA2NM_175077.3 linkc.20G>A p.Arg7Lys missense_variant Exon 2 of 8 NP_778252.1 Q9H6Q3-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLA2ENST00000262866.9 linkc.20G>A p.Arg7Lys missense_variant Exon 2 of 8 1 NM_032214.4 ENSP00000262866.4 Q9H6Q3-1
SLA2ENST00000360672.2 linkc.20G>A p.Arg7Lys missense_variant Exon 2 of 8 5 ENSP00000353890.2 Q9H6Q3-2

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461738
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727172
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.037
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
19
DANN
Benign
0.95
DEOGEN2
Benign
0.056
T;.
Eigen
Benign
-0.50
Eigen_PC
Benign
-0.31
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Benign
0.55
T;T
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.12
T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Uncertain
2.4
M;M
PrimateAI
Benign
0.48
T
PROVEAN
Benign
0.29
N;N
REVEL
Benign
0.15
Sift
Benign
0.66
T;T
Sift4G
Benign
0.53
T;T
Polyphen
0.0050
B;B
Vest4
0.40
MutPred
0.22
Gain of methylation at R7 (P = 0.0097);Gain of methylation at R7 (P = 0.0097);
MVP
0.84
MPC
0.23
ClinPred
0.52
D
GERP RS
3.3
Varity_R
0.089
gMVP
0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-35269719; COSMIC: COSV53410153; API