chr5-128084031-CGCTGGCCGCAGCCAGGGTGGAACT-C

Position:

• chr5-128084031-CGCTGGCCGCAGCCAGGGTGGAACT-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_001046.3(SLC12A2):​c.80_103del​(p.Leu27_Leu34del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC12A2 NM_001046.3 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.14

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001046.3.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A2	NM_001046.3	c.80_103del	p.Leu27_Leu34del	inframe_deletion	1/27	ENST00000262461.7	NP_001037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A2	ENST00000262461.7	c.80_103del	p.Leu27_Leu34del	inframe_deletion	1/27	1	NM_001046.3	ENSP00000262461	P4
SLC12A2	ENST00000343225.4	c.80_103del	p.Leu27_Leu34del	inframe_deletion	1/26	1		ENSP00000340878	A2
SLC12A2	ENST00000509205.5	c.80_103del	p.Leu27_Leu34del	inframe_deletion, NMD_transcript_variant	1/27	1		ENSP00000427109
SLC12A2	ENST00000628403.2	c.80_103del	p.Leu27_Leu34del	inframe_deletion	1/26	5		ENSP00000486323

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: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Dec 17, 2022

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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: rs1759931629; hg19: chr5-127419723;