rs697003

Variant names:

• chr1-211669734-C-G
• rs697003
• NM_002497.4:c.766-402G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-211669734-C-G
• chr1-211669734-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002497.4(NEK2):​c.766-402G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 152,098 control chromosomes in the GnomAD database, including 23,772 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (23772 hom., cov: 32)
• Consequence: NEK2 NM_002497.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis pigmentosa 67

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002497.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEK2	NM_002497.4	MANE Select	c.766-402G>C		intron	N/A	NP_002488.1
	NEK2	NM_001204182.2		c.766-402G>C		intron	N/A	NP_001191111.1
	NEK2	NM_001204183.2		c.766-402G>C		intron	N/A	NP_001191112.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEK2	ENST00000366999.9	TSL:1 MANE Select	c.766-402G>C		intron	N/A	ENSP00000355966.4
	NEK2	ENST00000540251.5	TSL:1	c.766-402G>C		intron	N/A	ENSP00000440237.2
	NEK2	ENST00000366998.4	TSL:1	c.766-402G>C		intron	N/A	ENSP00000355965.3

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84123 AN: 151980 Hom.: 23742 Cov.: 32

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.552

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.554 AC: 84199 AN: 152098 Hom.: 23772 Cov.: 32 AF XY: 0.560 AC XY: 41631 AN XY: 74352

African (AFR) AF: 0.594 AC: 24628 AN: 41484

American (AMR) AF: 0.646 AC: 9875 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1742 AN: 3472

East Asian (EAS) AF: 0.728 AC: 3765 AN: 5172

South Asian (SAS) AF: 0.627 AC: 3025 AN: 4824

European-Finnish (FIN) AF: 0.576 AC: 6084 AN: 10560

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.488 AC: 33197 AN: 67976

Other (OTH) AF: 0.559 AC: 1181 AN: 2114

Alfa AF: 0.529 Hom.: 2604

Bravo AF: 0.559

Asia WGS AF: 0.664 AC: 2308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.50
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs697003; hg19: chr1-211843076;