rs55635245

Variant names:

• chr1-211675465-A-C
• rs55635245
• NM_002497.4:c.15T>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002497.4(NEK2):​c.15T>G​(p.Ala5Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0603 in 1,612,816 control chromosomes in the GnomAD database, including 3,426 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.048 (253 hom., cov: 33)
  • Exomes 𝑓: 0.062 (3173 hom.)
• Consequence: NEK2 NM_002497.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.135
• 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-DT (HGNC:28085): (NEK2 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 1-211675465-A-C is Benign according to our data. Variant chr1-211675465-A-C is described in ClinVar as Benign. ClinVar VariationId is 403229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.135 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0967 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.15T>G	p.Ala5Ala	synonymous	Exon 1 of 8	NP_002488.1
	NEK2	NM_001204182.2		c.15T>G	p.Ala5Ala	synonymous	Exon 1 of 8	NP_001191111.1
	NEK2	NM_001204183.2		c.15T>G	p.Ala5Ala	synonymous	Exon 1 of 7	NP_001191112.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.0475 AC: 7236 AN: 152234 Hom.: 254 Cov.: 33

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0405

Gnomad FIN AF: 0.0274

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0631

Gnomad OTH AF: 0.0473

GnomAD2 exomes AF: 0.0573 AC: 14289 AN: 249186 AF XY: 0.0549

Gnomad AFR exome AF: 0.0118

Gnomad AMR exome AF: 0.138

Gnomad ASJ exome AF: 0.0312

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.0284

Gnomad NFE exome AF: 0.0607

Gnomad OTH exome AF: 0.0524

GnomAD4 exome AF: 0.0616 AC: 90006 AN: 1460464 Hom.: 3173 Cov.: 31 AF XY: 0.0605 AC XY: 43936 AN XY: 726534

African (AFR) AF: 0.0103 AC: 345 AN: 33448

American (AMR) AF: 0.132 AC: 5872 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.0312 AC: 816 AN: 26122

East Asian (EAS) AF: 0.000957 AC: 38 AN: 39690

South Asian (SAS) AF: 0.0438 AC: 3778 AN: 86180

European-Finnish (FIN) AF: 0.0310 AC: 1652 AN: 53344

Middle Eastern (MID) AF: 0.0487 AC: 266 AN: 5464

European-Non Finnish (NFE) AF: 0.0666 AC: 73963 AN: 1111280

Other (OTH) AF: 0.0543 AC: 3276 AN: 60310

GnomAD4 genome AF: 0.0475 AC: 7238 AN: 152352 Hom.: 253 Cov.: 33 AF XY: 0.0472 AC XY: 3517 AN XY: 74516

African (AFR) AF: 0.0144 AC: 600 AN: 41592

American (AMR) AF: 0.101 AC: 1544 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 117 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0412 AC: 199 AN: 4834

European-Finnish (FIN) AF: 0.0274 AC: 291 AN: 10626

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0632 AC: 4296 AN: 68018

Other (OTH) AF: 0.0468 AC: 99 AN: 2114

Alfa AF: 0.0531 Hom.: 114

Bravo AF: 0.0529

Asia WGS AF: 0.0180 AC: 65 AN: 3478

EpiCase AF: 0.0612

EpiControl AF: 0.0582

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.78
PhyloP100		-0.14
PromoterAI		0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs55635245; hg19: chr1-211848807; COSMIC: COSV108212036; COSMIC: COSV108212036;