rs886040968

Positions:

• chr5-128178663-ATGTCTGGTGGC-A

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001046.3(SLC12A2):​c.3076_3086del​(p.Val1026PhefsTer2) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC12A2 NM_001046.3 frameshift
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.92

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 Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 5-128178663-ATGTCTGGTGGC-A is Pathogenic according to our data. Variant chr5-128178663-ATGTCTGGTGGC-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 267304.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC12A2	NM_001046.3	c.3076_3086del	p.Val1026PhefsTer2	frameshift_variant	22/27	ENST00000262461.7
SLC12A2	NM_001256461.2	c.3028_3038del	p.Val1010PhefsTer2	frameshift_variant	21/26
SLC12A2	NR_046207.2	n.3265_3275del		non_coding_transcript_exon_variant	22/27
SLC12A2	XM_047417591.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC12A2	ENST00000262461.7	c.3076_3086del	p.Val1026PhefsTer2	frameshift_variant	22/27	1	NM_001046.3	P4

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Infant onset multiple organ failure Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

Undiagnosed Diseases Program Translational Research Laboratory, National Institutes of Health

Oct 01, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs886040968; hg19: chr5-127514355;