NM_002497.4:c.1320G>T

Variant names:

• chr1-211663444-C-A
• rs141984487
• NM_002497.4:c.1320G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002497.4(NEK2):​c.1320G>T​(p.Gln440His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q440K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NEK2 NM_002497.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.743
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEK2	NM_002497.4	c.1320G>T	p.Gln440His	missense_variant	Exon 8 of 8	ENST00000366999.9	NP_002488.1
NEK2	NM_001204182.2	c.1111+3662G>T		intron_variant	Intron 7 of 7		NP_001191111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEK2	ENST00000366999.9	c.1320G>T	p.Gln440His	missense_variant	Exon 8 of 8	1	NM_002497.4	ENSP00000355966.4
NEK2	ENST00000540251.5	c.1111+3662G>T		intron_variant	Intron 7 of 7	1		ENSP00000440237.2
NEK2	ENST00000462283.5	n.760G>T		non_coding_transcript_exon_variant	Exon 5 of 5	2
NEK2	ENST00000489633.1	n.*81G>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.066	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Uncertain	0.48	D
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.74
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.50
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.024	D
Polyphen		0.99	D
Vest4		0.51
MutPred		0.25		Gain of sheet (P = 0.0266);
MVP		0.91
MPC		1.1
ClinPred		0.95	D
GERP RS		4.5
Varity_R		0.17
gMVP		0.32
Mutation Taster		=64/36	polymorphism

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: rs141984487; hg19: chr1-211836786;