20-36615326-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032214.4(SLA2):​c.431G>A​(p.Arg144Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000799 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R144G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000081 ( 0 hom. )

Consequence

SLA2
NM_032214.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.588
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.041782796).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLA2NM_032214.4 linkc.431G>A p.Arg144Gln missense_variant Exon 6 of 8 ENST00000262866.9 NP_115590.1 Q9H6Q3-1
SLA2NM_175077.3 linkc.431G>A p.Arg144Gln missense_variant Exon 6 of 8 NP_778252.1 Q9H6Q3-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLA2ENST00000262866.9 linkc.431G>A p.Arg144Gln missense_variant Exon 6 of 8 1 NM_032214.4 ENSP00000262866.4 Q9H6Q3-1
SLA2ENST00000360672.2 linkc.431G>A p.Arg144Gln missense_variant Exon 6 of 8 5 ENSP00000353890.2 Q9H6Q3-2

Frequencies

GnomAD3 genomes
AF:
0.0000658
AC:
10
AN:
152090
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000578
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000478
AC:
12
AN:
251236
Hom.:
0
AF XY:
0.0000736
AC XY:
10
AN XY:
135830
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000616
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000814
AC:
119
AN:
1461870
Hom.:
0
Cov.:
31
AF XY:
0.0000866
AC XY:
63
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000935
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152208
Hom.:
0
Cov.:
32
AF XY:
0.0000941
AC XY:
7
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000579
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000116
Hom.:
0
Bravo
AF:
0.0000567
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000577
AC:
7
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 25, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.431G>A (p.R144Q) alteration is located in exon 6 (coding exon 5) of the SLA2 gene. This alteration results from a G to A substitution at nucleotide position 431, causing the arginine (R) at amino acid position 144 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.090
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
19
DANN
Benign
0.90
DEOGEN2
Benign
0.19
T;.
Eigen
Benign
-0.59
Eigen_PC
Benign
-0.43
FATHMM_MKL
Benign
0.28
N
LIST_S2
Benign
0.68
T;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.042
T;T
MetaSVM
Benign
-0.80
T
MutationAssessor
Benign
0.66
N;N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
0.45
N;N
REVEL
Benign
0.10
Sift
Benign
0.85
T;T
Sift4G
Benign
0.64
T;T
Polyphen
0.015
B;B
Vest4
0.23
MVP
0.83
MPC
0.29
ClinPred
0.045
T
GERP RS
1.9
Varity_R
0.16
gMVP
0.36

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

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

Other links and lift over

dbSNP: rs200208007; hg19: chr20-35243729; API