NM_001282211.2:c.25-4541T>C

Variant names:

• chr14-21027862-A-G
• rs1952524
• NM_001282211.2:c.25-4541T>C

Variant summary

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

The NM_001282211.2(NDRG2):​c.25-4541T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,030 control chromosomes in the GnomAD database, including 7,703 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 0.31 (7703 hom., cov: 32)
• Consequence: NDRG2 NM_001282211.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.374
• Publications: 4 publications found

Genes affected

NDRG2 (HGNC:14460): (NDRG family member 2) This gene is a member of the N-myc downregulated gene family which belongs to the alpha/beta hydrolase superfamily. The protein encoded by this gene is a cytoplasmic protein that may play a role in neurite outgrowth. This gene may be involved in glioblastoma carcinogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2017]

ENSG00000258604 (HGNC:):

TPPP2 (HGNC:19293): (tubulin polymerization promoting protein family member 2) Enables tubulin binding activity. Involved in regulation of flagellated sperm motility. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282211.2. 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
	NDRG2	NM_001282211.2		c.25-4541T>C		intron	N/A	NP_001269140.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDRG2	ENST00000403829.7	TSL:2	c.25-4541T>C		intron	N/A	ENSP00000385889.3
	NDRG2	ENST00000555026.5	TSL:5	c.-6-4541T>C		intron	N/A	ENSP00000451274.1
	ENSG00000258604	ENST00000532213.2	TSL:3	n.50-584A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47066 AN: 151912 Hom.: 7681 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.310 AC: 47135 AN: 152030 Hom.: 7703 Cov.: 32 AF XY: 0.309 AC XY: 22983 AN XY: 74306

African (AFR) AF: 0.387 AC: 16050 AN: 41468

American (AMR) AF: 0.205 AC: 3135 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 954 AN: 3470

East Asian (EAS) AF: 0.240 AC: 1239 AN: 5170

South Asian (SAS) AF: 0.172 AC: 826 AN: 4816

European-Finnish (FIN) AF: 0.388 AC: 4092 AN: 10560

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19978 AN: 67962

Other (OTH) AF: 0.292 AC: 616 AN: 2106

Alfa AF: 0.280 Hom.: 10524

Bravo AF: 0.300

Asia WGS AF: 0.235 AC: 816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.76
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1952524; hg19: chr14-21496021;