rs398122961

Positions:

• chr1-211671215-ACTCATACA-AT

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_002497.4(NEK2):​c.617_624delinsA​(p.Leu206HisfsTer5) 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 Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. LYEL206H?) has been classified as Likely pathogenic. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NEK2 NM_002497.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.99

Genes affected

NEK2 (HGNC:7745): (NIMA related kinase 2) This gene encodes a serine/threonine-protein kinase that is involved in mitotic regulation. This protein is localized to the centrosome, and undetectable during G1 phase, but accumulates progressively throughout the S phase, reaching maximal levels in late G2 phase. Alternatively spliced transcript variants encoding different isoforms with distinct C-termini have been noted for this gene. [provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-211671216-CTCATACA-T is Pathogenic according to our data. Variant chr1-211671216-CTCATACA-T is described in ClinVar as [Pathogenic]. Clinvar id is 91391.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK2	NM_002497.4	c.617_624delinsA	p.Leu206HisfsTer5	frameshift_variant	4/8	ENST00000366999.9
NEK2	NM_001204182.2	c.617_624delinsA	p.Leu206HisfsTer5	frameshift_variant	4/8
NEK2	NM_001204183.2	c.617_624delinsA	p.Leu206HisfsTer5	frameshift_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK2	ENST00000366999.9	c.617_624delinsA	p.Leu206HisfsTer5	frameshift_variant	4/8	1	NM_002497.4	P1
NEK2	ENST00000366998.4	c.617_624delinsA	p.Leu206HisfsTer5	frameshift_variant	4/7	1
NEK2	ENST00000540251.5	c.617_624delinsA	p.Leu206HisfsTer5	frameshift_variant	4/8	1
NEK2	ENST00000462283.5	n.62_69delinsA		non_coding_transcript_exon_variant	1/5	2

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

Retinitis pigmentosa 67 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 01, 2013

- -

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: rs398122961; hg19: chr1-211844558;