1-211663493-GC-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_002497.4(NEK2):c.1270del(p.Ala424LeufsTer13) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000684 in 1,461,618 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NEK2 NM_002497.4 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 3.85

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-211663493-GC-G is Pathogenic according to our data. Variant chr1-211663493-GC-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3028564.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK2	NM_002497.4	c.1270del	p.Ala424LeufsTer13	frameshift_variant	8/8	ENST00000366999.9
NEK2	NM_001204182.2	c.1111+3612del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK2	ENST00000366999.9	c.1270del	p.Ala424LeufsTer13	frameshift_variant	8/8	1	NM_002497.4	P1
NEK2	ENST00000540251.5	c.1111+3612del		intron_variant		1
NEK2	ENST00000462283.5	n.710del		non_coding_transcript_exon_variant	5/5	2
NEK2	ENST00000489633.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461618 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727120

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Retinal dystrophy Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

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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: rs1655077098; hg19: chr1-211836835;