chr14-90292547-G-T

Variant names:

• chr14-90292547-G-T
• rs2282032
• NM_017970.4:c.1842+150C>A

Variant summary

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

The NM_017970.4(NRDE2):​c.1842+150C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 773,908 control chromosomes in the GnomAD database, including 14,116 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 0.18 (2531 hom., cov: 32)
  • Exomes 𝑓: 0.19 (11585 hom.)
• Consequence: NRDE2 NM_017970.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56
• Publications: 22 publications found

Genes affected

NRDE2 (HGNC:20186): (NRDE-2, necessary for RNA interference, domain containing) Involved in several processes, including RNA splicing; negative regulation of RNA catabolic process; and positive regulation of RNA export from nucleus. Located in nuclear speck and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000287437 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRDE2	NM_017970.4	c.1842+150C>A		intron_variant	Intron 9 of 13	ENST00000354366.8	NP_060440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRDE2	ENST00000354366.8	c.1842+150C>A		intron_variant	Intron 9 of 13	1	NM_017970.4	ENSP00000346335.3

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27372 AN: 152056 Hom.: 2526 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.0812

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.187 AC: 116508 AN: 621734 Hom.: 11585 AF XY: 0.189 AC XY: 60470 AN XY: 320266

African (AFR) AF: 0.148 AC: 2361 AN: 15974

American (AMR) AF: 0.211 AC: 4421 AN: 20952

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 2519 AN: 14788

East Asian (EAS) AF: 0.0916 AC: 3019 AN: 32946

South Asian (SAS) AF: 0.226 AC: 11059 AN: 48942

European-Finnish (FIN) AF: 0.223 AC: 7719 AN: 34570

Middle Eastern (MID) AF: 0.167 AC: 379 AN: 2266

European-Non Finnish (NFE) AF: 0.189 AC: 79358 AN: 419570

Other (OTH) AF: 0.179 AC: 5673 AN: 31726

GnomAD4 genome AF: 0.180 AC: 27395 AN: 152174 Hom.: 2531 Cov.: 32 AF XY: 0.181 AC XY: 13461 AN XY: 74396

African (AFR) AF: 0.150 AC: 6244 AN: 41524

American (AMR) AF: 0.188 AC: 2875 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 568 AN: 3470

East Asian (EAS) AF: 0.0810 AC: 419 AN: 5172

South Asian (SAS) AF: 0.207 AC: 996 AN: 4822

European-Finnish (FIN) AF: 0.218 AC: 2311 AN: 10586

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13356 AN: 67986

Other (OTH) AF: 0.175 AC: 369 AN: 2114

Alfa AF: 0.190 Hom.: 12763

Bravo AF: 0.176

Asia WGS AF: 0.173 AC: 603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.5
DANN	Benign	0.73
PhyloP100		1.6
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: rs2282032; hg19: chr14-90758891;