Variant 1-150460125-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000369068.5(RPRD2):c.1219A>G(p.Thr407Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,613,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

RPRD2
ENST00000369068.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.629

Variant links:

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]

RPRD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07397398).

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPRD2	NM_015203.5 linkuse as main transcript	c.1219A>G	p.Thr407Ala	missense_variant	9/11	ENST00000369068.5	NP_056018.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPRD2	ENST00000369068.5 linkuse as main transcript	c.1219A>G	p.Thr407Ala	missense_variant	9/11	1	NM_015203.5	ENSP00000358064	P5	Q5VT52-1
RPRD2	ENST00000401000.8 linkuse as main transcript	c.1141A>G	p.Thr381Ala	missense_variant	8/10	1		ENSP00000383785	A2	Q5VT52-3
RPRD2	ENST00000492220.1 linkuse as main transcript	n.1391A>G		non_coding_transcript_exon_variant	9/11	5

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000441

AC:

AN:

249160

Hom.:

AF XY:

0.0000518

AC XY:

AN XY:

135172

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000531

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000397

AC:

AN:

1461690

Hom.:

Cov.:

AF XY:

0.0000454

AC XY:

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000423

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000662

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.1219A>G (p.T407A) alteration is located in exon 9 (coding exon 9) of the RPRD2 gene. This alteration results from a A to G substitution at nucleotide position 1219, causing the threonine (T) at amino acid position 407 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.52

CADD

Benign

9.5

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

.;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.0077

MetaRNN

Benign

0.074

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

.;L

MutationTaster

Benign

0.74

D;D;D

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.058

Sift

Uncertain

0.0020

D;D

Sift4G

Benign

0.16

T;D

Polyphen

0.0040

B;B

Vest4

0.13

MVP

0.082

MPC

0.19

ClinPred

0.11

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.37

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over