rs786204794

Positions:

• chr21-37714699-ATGG-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4_Supporting PP5

The NM_002240.5(KCNJ6):​c.455_457del​(p.Thr152del) variant causes a inframe deletion 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 Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KCNJ6 NM_002240.5 inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 10.0

Genes affected

KCNJ6 (HGNC:6267): (potassium inwardly rectifying channel subfamily J member 6) This gene encodes a member of the G protein-coupled inwardly-rectifying potassium channel family of inward rectifier potassium channels. This type of potassium channel allows a greater flow of potassium into the cell than out of it. These proteins modulate many physiological processes, including heart rate in cardiac cells and circuit activity in neuronal cells, through G-protein coupled receptor stimulation. Mutations in this gene are associated with Keppen-Lubinsky Syndrome, a rare condition characterized by severe developmental delay, facial dysmorphism, and intellectual disability. [provided by RefSeq, Apr 2015]

KCNJ6-AS1 (HGNC:):

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_002240.5. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 21-37714699-ATGG-A is Pathogenic according to our data. Variant chr21-37714699-ATGG-A is described in ClinVar as [Pathogenic]. Clinvar id is 189254.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr21-37714699-ATGG-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ6	NM_002240.5	c.455_457del	p.Thr152del	inframe_deletion	3/4	ENST00000609713.2	NP_002231.1
KCNJ6-AS1	NR_183540.1	n.1146_1148del		non_coding_transcript_exon_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ6	ENST00000609713.2	c.455_457del	p.Thr152del	inframe_deletion	3/4	1	NM_002240.5	ENSP00000477437	P1
KCNJ6-AS1	ENST00000711629.1	n.739_741del		non_coding_transcript_exon_variant	3/7
KCNJ6	ENST00000645093.1	c.455_457del	p.Thr152del	inframe_deletion	4/5			ENSP00000493772	P1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Keppen-Lubinsky syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 05, 2015

- -

Computational scores

Source: dbNSFP v4.3

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: rs786204794; hg19: chr21-39087002;