20-36633612-G-C

Variant names:

• chr20-36633612-G-C
• rs757714870
• NM_032214.4:c.209C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032214.4(SLA2):​c.209C>G​(p.Thr70Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. T70M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SLA2 NM_032214.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.641
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.124663204).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032214.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLA2	NM_032214.4	MANE Select	c.209C>G	p.Thr70Arg	missense	Exon 4 of 8	NP_115590.1	Q9H6Q3-1
	SLA2	NM_175077.3		c.209C>G	p.Thr70Arg	missense	Exon 4 of 8	NP_778252.1	Q9H6Q3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLA2	ENST00000262866.9	TSL:1 MANE Select	c.209C>G	p.Thr70Arg	missense	Exon 4 of 8	ENSP00000262866.4	Q9H6Q3-1
	SLA2	ENST00000948638.1		c.209C>G	p.Thr70Arg	missense	Exon 4 of 9	ENSP00000618697.1
	SLA2	ENST00000948639.1		c.209C>G	p.Thr70Arg	missense	Exon 3 of 7	ENSP00000618698.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461612 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 727110

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111798

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Benign	0.89
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.080	N
PhyloP100		0.64
PrimateAI	Benign	0.37	T
PROVEAN	Benign	1.9	N
REVEL	Benign	0.056
Sift	Benign	0.68	T
Sift4G	Benign	0.86	T
Polyphen		0.0040	B
Vest4		0.40
MutPred		0.32		Loss of sheet (P = 0.1158)
MVP		0.59
MPC		0.36
ClinPred		0.33	T
GERP RS		4.0
Varity_R		0.14
gMVP		0.53
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs757714870; hg19: chr20-35262015;