rs2228112

Positions:

• chr5-128134167-A-C
• chr5-128134167-A-G
• chr5-128134167-A-T

Variant summary

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

The NM_001046.3(SLC12A2):​c.1191A>C​(p.Glu397Asp) variant causes a missense, splice region 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. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC12A2 NM_001046.3 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110

Genes affected

SLC12A2 (HGNC:10911): (solute carrier family 12 member 2) The protein encoded by this gene mediates sodium and chloride transport and reabsorption. The encoded protein is a membrane protein and is important in maintaining proper ionic balance and cell volume. This protein is phosphorylated in response to DNA damage. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

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=0.11293569).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A2	NM_001046.3	c.1191A>C	p.Glu397Asp	missense_variant, splice_region_variant	6/27	ENST00000262461.7	NP_001037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A2	ENST00000262461.7	c.1191A>C	p.Glu397Asp	missense_variant, splice_region_variant	6/27	1	NM_001046.3	ENSP00000262461.2
SLC12A2	ENST00000343225.4	c.1191A>C	p.Glu397Asp	missense_variant, splice_region_variant	6/26	1		ENSP00000340878.4
SLC12A2	ENST00000509205.5	n.1191A>C		splice_region_variant, non_coding_transcript_exon_variant	6/27	1		ENSP00000427109.1
SLC12A2	ENST00000628403.2	c.1191A>C	p.Glu397Asp	missense_variant, splice_region_variant	6/26	5		ENSP00000486323.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 20

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.72	D;.;.
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.79	T;T;T
M_CAP	Uncertain	0.095	D
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Uncertain	0.46	D
MutationAssessor	Benign	0.87	L;.;L
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.92	N;.;N
REVEL	Uncertain	0.30
Sift	Benign	0.23	T;.;T
Sift4G	Benign	0.32	T;T;T
Polyphen		0.0070	B;.;B
Vest4		0.14
MutPred		0.47		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP		0.59
MPC		0.63
ClinPred		0.17	T
GERP RS		2.5
Varity_R		0.081
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

LitVar

Other links and lift over

dbSNP: rs2228112; hg19: chr5-127469859;