Variant 1-150471125-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000369068.5(RPRD2):c.2177G>A(p.Arg726Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,704 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R726W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

RPRD2
ENST00000369068.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.69

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPRD2	NM_015203.5 linkuse as main transcript	c.2177G>A	p.Arg726Gln	missense_variant	11/11	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.2177G>A	p.Arg726Gln	missense_variant	11/11	1	NM_015203.5	ENSP00000358064	P5	Q5VT52-1
RPRD2	ENST00000401000.8 linkuse as main transcript	c.2099G>A	p.Arg700Gln	missense_variant	10/10	1		ENSP00000383785	A2	Q5VT52-3
RPRD2	ENST00000492220.1 linkuse as main transcript	n.2349G>A		non_coding_transcript_exon_variant	11/11	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461704

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000126

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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 29, 2021

The c.2177G>A (p.R726Q) alteration is located in exon 11 (coding exon 11) of the RPRD2 gene. This alteration results from a G to A substitution at nucleotide position 2177, causing the arginine (R) at amino acid position 726 to be replaced by a glutamine (Q). 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

Pathogenic

0.89

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.17

.;T

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;D

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.45

T;T

MetaSVM

Benign

-0.31

MutationAssessor

Benign

1.0

.;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.4

N;N

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.15

T;T

Polyphen

1.0

D;D

Vest4

0.52

MutPred

0.17

.;Gain of glycosylation at T723 (P = 0.0674);

MVP

0.72

MPC

0.82

ClinPred

0.95

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.49

gMVP

0.62

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