Variant 1-211663447-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002497.4(NEK2):c.1317A>G(p.Arg439=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 1,612,166 control chromosomes in the GnomAD database, including 51,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6530 hom., cov: 32)

Exomes 𝑓: 0.24 ( 44960 hom. )

Consequence

NEK2
NM_002497.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.01

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 Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 1-211663447-T-C is Benign according to our data. Variant chr1-211663447-T-C is described in ClinVar as [Benign]. Clinvar id is 403226.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK2	NM_002497.4 linkuse as main transcript	c.1317A>G	p.Arg439=	synonymous_variant	8/8	ENST00000366999.9	NP_002488.1
NEK2	NM_001204182.2 linkuse as main transcript	c.1111+3659A>G		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.1317A>G	p.Arg439=	synonymous_variant	8/8	1	NM_002497.4	ENSP00000355966	P1	P51955-1
NEK2	ENST00000540251.5 linkuse as main transcript	c.1111+3659A>G		intron_variant		1		ENSP00000440237
NEK2	ENST00000462283.5 linkuse as main transcript	n.757A>G		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43271

AN:

151988

Hom.:

6510

Cov.:

show subpopulations

Gnomad AFR

AF:

0.370

Gnomad AMI

AF:

0.301

Gnomad AMR

AF:

0.319

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.261

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.247

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.236

Gnomad OTH

AF:

0.274

GnomAD3 exomes

AF:

0.268

AC:

66655

AN:

248272

Hom.:

9363

AF XY:

0.262

AC XY:

35203

AN XY:

134136

show subpopulations

Gnomad AFR exome

AF:

0.378

Gnomad AMR exome

AF:

0.352

Gnomad ASJ exome

AF:

0.217

Gnomad EAS exome

AF:

0.273

Gnomad SAS exome

AF:

0.283

Gnomad FIN exome

AF:

0.259

Gnomad NFE exome

AF:

0.230

Gnomad OTH exome

AF:

0.259

GnomAD4 exome

AF:

0.245

AC:

357711

AN:

1460060

Hom.:

44960

Cov.:

AF XY:

0.245

AC XY:

177565

AN XY:

726172

show subpopulations

Gnomad4 AFR exome

AF:

0.376

Gnomad4 AMR exome

AF:

0.349

Gnomad4 ASJ exome

AF:

0.217

Gnomad4 EAS exome

AF:

0.272

Gnomad4 SAS exome

AF:

0.281

Gnomad4 FIN exome

AF:

0.259

Gnomad4 NFE exome

AF:

0.233

Gnomad4 OTH exome

AF:

0.254

GnomAD4 genome

AF:

0.285

AC:

43342

AN:

152106

Hom.:

6530

Cov.:

AF XY:

0.284

AC XY:

21132

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.370

Gnomad4 AMR

AF:

0.319

Gnomad4 ASJ

AF:

0.209

Gnomad4 EAS

AF:

0.260

Gnomad4 SAS

AF:

0.299

Gnomad4 FIN

AF:

0.247

Gnomad4 NFE

AF:

0.236

Gnomad4 OTH

AF:

0.277

Alfa

AF:

0.253

Hom.:

2181

Bravo

AF:

0.292

Asia WGS

AF:

0.325

AC:

1130

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Retinal dystrophy

Benign:1

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.2

DANN

Benign

0.67

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