chr14-21027862-A-G

Position:

• chr14-21027862-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000533984.1(ENSG00000258604):​n.174-1079A>G variant causes a intron, non coding transcript 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: ENST00000533984.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.374

Genes affected

(HGNC:):

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]

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDRG2	NM_001282211.2	c.25-4541T>C		intron_variant			NP_001269140.1
TPPP2	XM_017020966.2	c.-69-2651A>G		intron_variant			XP_016876455.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000533984.1	n.174-1079A>G		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.292

Alfa AF: 0.276 Hom.: 8032

Bravo AF: 0.300

Asia WGS AF: 0.235 AC: 816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1952524; hg19: chr14-21496021;