rs398122961

Variant names:

• chr1-211671216-CTCATACA-T
• rs398122961
• NM_002497.4:c.617_624delTGTATGAGinsA

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_002497.4(NEK2):​c.617_624delTGTATGAGinsA​(p.Leu206HisfsTer5) variant causes a frameshift, synonymous 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, synonymous
• 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 Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• 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 rank	MANE	Protein	UniProt
NEK2	NM_002497.4	c.617_624delTGTATGAGinsA	p.Leu206HisfsTer5	frameshift_variant, synonymous_variant	Exon 4 of 8	ENST00000366999.9	NP_002488.1
NEK2	NM_001204182.2	c.617_624delTGTATGAGinsA	p.Leu206HisfsTer5	frameshift_variant, synonymous_variant	Exon 4 of 8		NP_001191111.1
NEK2	NM_001204183.2	c.617_624delTGTATGAGinsA	p.Leu206HisfsTer5	frameshift_variant, synonymous_variant	Exon 4 of 7		NP_001191112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEK2	ENST00000366999.9	c.617_624delTGTATGAGinsA	p.Leu206HisfsTer5	frameshift_variant, synonymous_variant	Exon 4 of 8	1	NM_002497.4	ENSP00000355966.4
NEK2	ENST00000540251.5	c.617_624delTGTATGAGinsA	p.Leu206HisfsTer5	frameshift_variant, synonymous_variant	Exon 4 of 8	1		ENSP00000440237.2
NEK2	ENST00000366998.4	c.617_624delTGTATGAGinsA	p.Leu206HisfsTer5	frameshift_variant, synonymous_variant	Exon 4 of 7	1		ENSP00000355965.3
NEK2	ENST00000462283.5	n.62_69delTGTATGAGinsA		non_coding_transcript_exon_variant	Exon 1 of 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

Oct 01, 2013

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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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: rs398122961; hg19: chr1-211844558;