19-47457006-C-G

Position:

• chr19-47457006-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015063.3(SLC8A2):​c.1264G>C​(p.Glu422Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC8A2 NM_015063.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.850

Genes affected

SLC8A2 (HGNC:11069): (solute carrier family 8 member A2) Predicted to enable calcium:cation antiporter activity involved in regulation of postsynaptic cytosolic calcium ion concentration and calcium:sodium antiporter activity. Predicted to be involved in several processes, including inorganic cation transmembrane transport; learning or memory; and regulation of short-term neuronal synaptic plasticity. Predicted to act upstream of or within several processes, including modulation of chemical synaptic transmission; regulation of action potential firing pattern; and response to ischemia. Part of presynapse. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

SLC8A2 (HGNC:):

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=0.1489011).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC8A2	NM_015063.3	c.1264G>C	p.Glu422Gln	missense_variant	3/10	ENST00000236877.11	NP_055878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC8A2	ENST00000236877.11	c.1264G>C	p.Glu422Gln	missense_variant	3/10	1	NM_015063.3	ENSP00000236877.5
SLC8A2	ENST00000542837.2	c.532G>C	p.Glu178Gln	missense_variant	2/9	2		ENSP00000437536.1
SLC8A2	ENST00000539381.5	n.76-9019G>C		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.1264G>C (p.E422Q) alteration is located in exon 3 (coding exon 2) of the SLC8A2 gene. This alteration results from a G to C substitution at nucleotide position 1264, causing the glutamic acid (E) at amino acid position 422 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	0.10
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;.
Eigen	Benign	-0.067
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.0	L;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0040	D;D
Sift4G	Benign	0.066	T;T
Polyphen		0.69	P;.
Vest4		0.081
MutPred		0.59		Gain of sheet (P = 0.1208);.;
MVP		0.42
ClinPred		0.45	T
GERP RS		3.7
Varity_R		0.30
gMVP		0.60

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: chr19-47960263;