rs786204794

Variant names:

• chr21-37714699-ATGG-A
• rs786204794
• NM_002240.5:c.455_457delCCA

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4_Supporting PP5

The NM_002240.5(KCNJ6):​c.455_457delCCA​(p.Thr152del) variant causes a disruptive 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 disruptive_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 10.0
• Publications: 4 publications found

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:):

KCNJ6-AS1 (HGNC:41352): (KCNJ6 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 VariationId is 189254.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ6	NM_002240.5	c.455_457delCCA	p.Thr152del	disruptive_inframe_deletion	Exon 3 of 4	ENST00000609713.2	NP_002231.1
KCNJ6-AS1	NR_183540.1	n.1146_1148delGGT		non_coding_transcript_exon_variant	Exon 4 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ6	ENST00000609713.2	c.455_457delCCA	p.Thr152del	disruptive_inframe_deletion	Exon 3 of 4	1	NM_002240.5	ENSP00000477437.1
KCNJ6	ENST00000645093.1	c.455_457delCCA	p.Thr152del	disruptive_inframe_deletion	Exon 4 of 5			ENSP00000493772.1
KCNJ6-AS1	ENST00000711629.1	n.739_741delGGT		non_coding_transcript_exon_variant	Exon 3 of 7
KCNJ6-AS1	ENST00000838485.1	n.217-1423_217-1421delGGT		intron_variant	Intron 2 of 5

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

Feb 05, 2015

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		10
Mutation Taster		=21/79	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs786204794; hg19: chr21-39087002;