rs12029359

Positions:

• chr1-150460326-G-A

Variant summary

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

The NM_015203.5(RPRD2):​c.1411+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,600,990 control chromosomes in the GnomAD database, including 32,685 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 0.16 (2439 hom., cov: 31)
  • Exomes 𝑓: 0.20 (30246 hom.)
• Consequence: RPRD2 NM_015203.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420

Genes affected

RPRD2 (HGNC:29039): (regulation of nuclear pre-mRNA domain containing 2) Predicted to enable RNA polymerase II complex binding activity. Predicted to be involved in mRNA 3'-end processing. Part of RNA polymerase II, holoenzyme. [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=-0.7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPRD2	NM_015203.5	c.1411+9G>A		intron_variant		ENST00000369068.5	NP_056018.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPRD2	ENST00000369068.5	c.1411+9G>A		intron_variant		1	NM_015203.5	ENSP00000358064	P5
RPRD2	ENST00000401000.8	c.1333+9G>A		intron_variant		1		ENSP00000383785	A2
RPRD2	ENST00000492220.1	n.1583+9G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24921 AN: 152098 Hom.: 2437 Cov.: 31

Gnomad AFR AF: 0.0539

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.198

GnomAD3 exomes AF: 0.189 AC: 44319 AN: 234696 Hom.: 4517 AF XY: 0.196 AC XY: 24874 AN XY: 127002

Gnomad AFR exome AF: 0.0471

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.316

Gnomad EAS exome AF: 0.158

Gnomad SAS exome AF: 0.216

Gnomad FIN exome AF: 0.238

Gnomad NFE exome AF: 0.208

Gnomad OTH exome AF: 0.210

GnomAD4 exome AF: 0.200 AC: 290173 AN: 1448774 Hom.: 30246 Cov.: 31 AF XY: 0.203 AC XY: 146024 AN XY: 719846

Gnomad4 AFR exome AF: 0.0458

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.310

Gnomad4 EAS exome AF: 0.178

Gnomad4 SAS exome AF: 0.216

Gnomad4 FIN exome AF: 0.236

Gnomad4 NFE exome AF: 0.203

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.164 AC: 24932 AN: 152216 Hom.: 2439 Cov.: 31 AF XY: 0.165 AC XY: 12305 AN XY: 74406

Gnomad4 AFR AF: 0.0538

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.199

Alfa AF: 0.208 Hom.: 3701

Bravo AF: 0.154

Asia WGS AF: 0.230 AC: 800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.9
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs12029359; hg19: chr1-150432802; COSMIC: COSV64822862;