Genetic Variant SLA2:p.Pro44Leu (chr20-36634550-G-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_032214.4(SLA2):c.131C>T(p.Pro44Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00198 in 1,611,548 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 16 hom. )

Consequence

SLA2
NM_032214.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.64

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013395965).

BP6

Variant 20-36634550-G-A is Benign according to our data. Variant chr20-36634550-G-A is described in ClinVar as [Benign]. Clinvar id is 781751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLA2	NM_032214.4 link	c.131C>T	p.Pro44Leu	missense_variant	Exon 3 of 8	ENST00000262866.9	NP_115590.1	Q9H6Q3-1
SLA2	NM_175077.3 link	c.131C>T	p.Pro44Leu	missense_variant	Exon 3 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.131C>T	p.Pro44Leu	missense_variant	Exon 3 of 8	1	NM_032214.4	ENSP00000262866.4		Q9H6Q3-1
SLA2	ENST00000360672.2 link	c.131C>T	p.Pro44Leu	missense_variant	Exon 3 of 8	5		ENSP00000353890.2		Q9H6Q3-2

Frequencies

GnomAD3 genomes

AF:

0.00209

AC:

318

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.0231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00229

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00265

AC:

659

AN:

249058

Hom.:

AF XY:

0.00289

AC XY:

390

AN XY:

134732

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.0234

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.00149

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00268

Gnomad OTH exome

AF:

0.00398

GnomAD4 exome

AF:

0.00197

AC:

2875

AN:

1459220

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

1513

AN XY:

725630

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.00176

Gnomad4 ASJ exome

AF:

0.0236

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00160

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.00154

Gnomad4 OTH exome

AF:

0.00365

GnomAD4 genome

AF:

0.00209

AC:

318

AN:

152328

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

148

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000240

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.0231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.00229

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00321

Hom.:

Bravo

AF:

0.00215

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00384

AC:

ExAC

AF:

0.00260

AC:

316

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00504

EpiControl

AF:

0.00517

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

- -

Jul 21, 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

0.20

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;.

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.050

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-7.2

D;D

REVEL

Uncertain

0.36

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

1.0

D;D

Vest4

0.60

MVP

0.79

MPC

0.85

ClinPred

0.067

GERP RS

4.9

Varity_R

0.72

gMVP

0.69

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.

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