Variant 1-211663507-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_002497.4(NEK2):c.1257T>C(p.Ala419=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000181 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00095 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

NEK2
NM_002497.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.117

Variant links:

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]

NEK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 1-211663507-A-G is Benign according to our data. Variant chr1-211663507-A-G is described in ClinVar as [Benign]. Clinvar id is 782234.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.117 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK2	NM_002497.4 linkuse as main transcript	c.1257T>C	p.Ala419=	synonymous_variant	8/8	ENST00000366999.9	NP_002488.1
NEK2	NM_001204182.2 linkuse as main transcript	c.1111+3599T>C		intron_variant			NP_001191111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEK2	ENST00000366999.9 linkuse as main transcript	c.1257T>C	p.Ala419=	synonymous_variant	8/8	1	NM_002497.4	ENSP00000355966	P1	P51955-1
NEK2	ENST00000540251.5 linkuse as main transcript	c.1111+3599T>C		intron_variant		1		ENSP00000440237
NEK2	ENST00000462283.5 linkuse as main transcript	n.697T>C		non_coding_transcript_exon_variant	5/5	2
NEK2	ENST00000489633.1 linkuse as main transcript			downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000933

AC:

142

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00330

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000231

AC:

AN:

250804

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135586

show subpopulations

Gnomad AFR exome

AF:

0.00302

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000101

AC:

148

AN:

1461642

Hom.:

Cov.:

AF XY:

0.0000908

AC XY:

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.00367

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000945

AC:

144

AN:

152340

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00334

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000477

Hom.:

Bravo

AF:

0.00109

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 13, 2023

- -

NEK2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 15, 2019

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

-0.44

CADD

Benign

6.6

DANN

Benign

0.73

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over