Genetic Variant SLA2:p.Val210Met (chr20-36614342-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032214.4(SLA2):c.628G>A(p.Val210Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00451 in 1,614,150 control chromosomes in the GnomAD database, including 300 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.025 ( 169 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 131 hom. )

Consequence

SLA2
NM_032214.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.37

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]

SLA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019907653).

BP6

Variant 20-36614342-C-T is Benign according to our data. Variant chr20-36614342-C-T is described in ClinVar as [Benign]. Clinvar id is 781498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLA2	NM_032214.4 link	c.628G>A	p.Val210Met	missense_variant	Exon 7 of 8	ENST00000262866.9	NP_115590.1	Q9H6Q3-1
SLA2	NM_175077.3 link	c.578G>A	p.Cys193Tyr	missense_variant	Exon 7 of 8		NP_778252.1	Q9H6Q3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLA2	ENST00000262866.9 link	c.628G>A	p.Val210Met	missense_variant	Exon 7 of 8	1	NM_032214.4	ENSP00000262866.4		Q9H6Q3-1
SLA2	ENST00000360672.2 link	c.578G>A	p.Cys193Tyr	missense_variant	Exon 7 of 8	5		ENSP00000353890.2		Q9H6Q3-2

Frequencies

GnomAD3 genomes

AF:

0.0252

AC:

3838

AN:

152156

Hom.:

168

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0875

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.0211

GnomAD3 exomes

AF:

0.00680

AC:

1711

AN:

251446

Hom.:

AF XY:

0.00489

AC XY:

664

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.0935

Gnomad AMR exome

AF:

0.00422

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000588

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00235

AC:

3434

AN:

1461876

Hom.:

131

Cov.:

AF XY:

0.00200

AC XY:

1451

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0841

Gnomad4 AMR exome

AF:

0.00485

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000406

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000423

Gnomad4 OTH exome

AF:

0.00502

GnomAD4 genome

AF:

0.0253

AC:

3848

AN:

152274

Hom.:

169

Cov.:

AF XY:

0.0243

AC XY:

1811

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0875

Gnomad4 AMR

AF:

0.0105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.0209

Alfa

AF:

0.00436

Hom.:

Bravo

AF:

0.0291

ESP6500AA

AF:

0.0849

AC:

374

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00851

AC:

1033

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 27, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.26

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.98

PROVEAN

Benign

-0.28

REVEL

Benign

0.18

Sift

Uncertain

0.016

Sift4G

Benign

0.33

Polyphen

0.0090

Vest4

0.40

MVP

0.90

ClinPred

0.012

GERP RS

5.4

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over