NM_002512.4:c.126+430G>C

Variant names:

• chr17-51167386-G-C
• rs4605213
• NM_002512.4:c.126+430G>C

Variant summary

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

The NM_002512.4(NME2):​c.126+430G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 221,690 control chromosomes in the GnomAD database, including 25,388 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 0.48 (21207 hom., cov: 32)
  • Exomes 𝑓: 0.34 (4181 hom.)
• Consequence: NME2 NM_002512.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• Publications: 42 publications found

Genes affected

NME2 (HGNC:7850): (NME/NM23 nucleoside diphosphate kinase 2) Nucleoside diphosphate kinase (NDK) exists as a hexamer composed of 'A' (encoded by NME1) and 'B' (encoded by this gene) isoforms. Multiple alternatively spliced transcript variants have been found for this gene. Read-through transcription from the neighboring upstream gene (NME1) generates naturally-occurring transcripts (NME1-NME2) that encode a fusion protein comprised of sequence sharing identity with each individual gene product. [provided by RefSeq, Nov 2010]

NME1-NME2 (HGNC:33531): (NME1-NME2 readthrough) This locus represents naturally occurring read-through transcription between the neighboring NME1 and NME2 genes. The significance of this read-through transcription and the function of the resulting protein product have not yet been determined. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Nov 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002512.4. 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
	NME2	NM_002512.4	MANE Select	c.126+430G>C		intron	N/A	NP_002503.1	P22392-1
	NME1-NME2	NM_001018136.3		c.471+430G>C		intron	N/A	NP_001018146.1
	NME2	NM_001018137.3		c.126+430G>C		intron	N/A	NP_001018147.1	Q6FHN3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME2	ENST00000512737.6	TSL:1 MANE Select	c.126+430G>C		intron	N/A	ENSP00000421064.1	P22392-1
	NME1-NME2	ENST00000393193.6	TSL:2	c.471+430G>C		intron	N/A	ENSP00000376889.2
	NME2	ENST00000393190.4	TSL:1	c.126+430G>C		intron	N/A	ENSP00000376886.1	P22392-1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72301 AN: 152030 Hom.: 21154 Cov.: 32

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.427

GnomAD4 exome AF: 0.337 AC: 23437 AN: 69542 Hom.: 4181 AF XY: 0.322 AC XY: 11948 AN XY: 37162

African (AFR) AF: 0.791 AC: 334 AN: 422

American (AMR) AF: 0.364 AC: 609 AN: 1674

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 514 AN: 1516

East Asian (EAS) AF: 0.209 AC: 99 AN: 474

South Asian (SAS) AF: 0.241 AC: 3529 AN: 14658

European-Finnish (FIN) AF: 0.344 AC: 1609 AN: 4678

Middle Eastern (MID) AF: 0.384 AC: 96 AN: 250

European-Non Finnish (NFE) AF: 0.363 AC: 15219 AN: 41972

Other (OTH) AF: 0.366 AC: 1428 AN: 3898

GnomAD4 genome AF: 0.476 AC: 72404 AN: 152148 Hom.: 21207 Cov.: 32 AF XY: 0.465 AC XY: 34582 AN XY: 74382

African (AFR) AF: 0.839 AC: 34856 AN: 41524

American (AMR) AF: 0.376 AC: 5750 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1122 AN: 3468

East Asian (EAS) AF: 0.226 AC: 1171 AN: 5180

South Asian (SAS) AF: 0.214 AC: 1032 AN: 4824

European-Finnish (FIN) AF: 0.323 AC: 3426 AN: 10594

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23775 AN: 67962

Other (OTH) AF: 0.424 AC: 893 AN: 2108

Alfa AF: 0.372 Hom.: 6261

Bravo AF: 0.497

Asia WGS AF: 0.303 AC: 1059 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.3
DANN	Benign	0.52
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs4605213; hg19: chr17-49244747;