10-62198207-T-A

Variant names:

• chr10-62198207-T-A
• NM_145307.4:c.1531A>T
• RTKN2 p.Lys511*

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_145307.4(RTKN2):​c.1531A>T​(p.Lys511*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RTKN2 NM_145307.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 0 publications found

Genes affected

RTKN2 (HGNC:19364): (rhotekin 2) Involved in negative regulation of intrinsic apoptotic signaling pathway; positive regulation of NF-kappaB transcription factor activity; and positive regulation of NIK/NF-kappaB signaling. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RTKN2 Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145307.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTKN2	NM_145307.4	MANE Select	c.1531A>T	p.Lys511*	stop_gained	Exon 12 of 12	NP_660350.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTKN2	ENST00000373789.8	TSL:1 MANE Select	c.1531A>T	p.Lys511*	stop_gained	Exon 12 of 12	ENSP00000362894.3	Q8IZC4-1
	RTKN2	ENST00000955691.1		c.1636A>T	p.Lys546*	stop_gained	Exon 14 of 14	ENSP00000625750.1
	RTKN2	ENST00000919899.1		c.1594A>T	p.Lys532*	stop_gained	Exon 13 of 13	ENSP00000589958.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.58	D
BayesDel_noAF	Pathogenic	0.60
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.97	D
PhyloP100		2.0
Mutation Taster		=12/188	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-63957966;