1-211658657-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The ENST00000540251.5(NEK2):c.1167G>A(p.Ter389=) variant causes a stop retained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000428 in 413,578 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00048 (2 hom.)
• Consequence: NEK2 ENST00000540251.5 stop_retained
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.758

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 Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BP6: Variant 1-211658657-C-T is Benign according to our data. Variant chr1-211658657-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3046446.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.758 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK2	NM_001204182.2	c.1167G>A	p.Ter389=	stop_retained_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK2	ENST00000540251.5	c.1167G>A	p.Ter389=	stop_retained_variant	8/8	1

Frequencies

GnomAD3 genomes AF: 0.000295 AC: 36 AN: 121960 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000634

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00270

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000477

Gnomad OTH AF: 0.000608

GnomAD3 exomes AF: 0.000376 AC: 44 AN: 117006 Hom.: 0 AF XY: 0.000509 AC XY: 33 AN XY: 64794

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000219

Gnomad ASJ exome AF: 0.000128

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00167

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000236

Gnomad OTH exome AF: 0.000276

GnomAD4 exome AF: 0.000484 AC: 141 AN: 291534 Hom.: 2 Cov.: 0 AF XY: 0.000646 AC XY: 108 AN XY: 167178

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000232

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00214

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000327

Gnomad4 OTH exome AF: 0.000295

GnomAD4 genome AF: 0.000295 AC: 36 AN: 122044 Hom.: 0 Cov.: 29 AF XY: 0.000389 AC XY: 22 AN XY: 56530

Gnomad4 AFR AF: 0.0000632

Gnomad4 AMR AF: 0.00269

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000477

Gnomad4 OTH AF: 0.000601

Alfa AF: 0.0000959 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

NEK2-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 07, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	11
Dann	Benign	0.27

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs533273372; hg19: chr1-211831999;