20-36641316-C-T

Variant names:

• chr20-36641316-C-T
• NM_032214.4:c.20G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19

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

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
SLA2	NM_032214.4	c.20G>A	p.Arg7Lys	missense_variant	Exon 2 of 8	ENST00000262866.9	NP_115590.1
SLA2	NM_175077.3	c.20G>A	p.Arg7Lys	missense_variant	Exon 2 of 8		NP_778252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLA2	ENST00000262866.9	c.20G>A	p.Arg7Lys	missense_variant	Exon 2 of 8	1	NM_032214.4	ENSP00000262866.4
SLA2	ENST00000360672.2	c.20G>A	p.Arg7Lys	missense_variant	Exon 2 of 8	5		ENSP00000353890.2

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

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;