chr1-211675465-A-T

Variant names:

• chr1-211675465-A-T
• NM_002497.4:c.15T>A
• NEK2 p.Ala5Ala

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002497.4(NEK2):​c.15T>A​(p.Ala5Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A5A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NEK2 NM_002497.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• Publications: 0 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-DT (HGNC:28085): (NEK2 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-0.135 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEK2	NM_002497.4	MANE Select	c.15T>A	p.Ala5Ala	synonymous	Exon 1 of 8	NP_002488.1	P51955-1
	NEK2	NM_001204182.2		c.15T>A	p.Ala5Ala	synonymous	Exon 1 of 8	NP_001191111.1	F6U4U2
	NEK2	NM_001204183.2		c.15T>A	p.Ala5Ala	synonymous	Exon 1 of 7	NP_001191112.1	P51955-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEK2	ENST00000366999.9	TSL:1 MANE Select	c.15T>A	p.Ala5Ala	synonymous	Exon 1 of 8	ENSP00000355966.4	P51955-1
	NEK2	ENST00000540251.5	TSL:1	c.15T>A	p.Ala5Ala	synonymous	Exon 1 of 8	ENSP00000440237.2	F6U4U2
	NEK2	ENST00000366998.4	TSL:1	c.15T>A	p.Ala5Ala	synonymous	Exon 1 of 7	ENSP00000355965.3	P51955-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Benign	0.90
PhyloP100		-0.14
PromoterAI		-0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-211848807;