1-150464611-C-T

Position:

• chr1-150464611-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000369068.5(RPRD2):​c.1496C>T​(p.Ala499Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: RPRD2 ENST00000369068.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.75

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14758962).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPRD2	NM_015203.5	c.1496C>T	p.Ala499Val	missense_variant	10/11	ENST00000369068.5	NP_056018.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPRD2	ENST00000369068.5	c.1496C>T	p.Ala499Val	missense_variant	10/11	1	NM_015203.5	ENSP00000358064	P5
RPRD2	ENST00000401000.8	c.1418C>T	p.Ala473Val	missense_variant	9/10	1		ENSP00000383785	A2
RPRD2	ENST00000492220.1	n.1668C>T		non_coding_transcript_exon_variant	10/11	5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2023

The c.1496C>T (p.A499V) alteration is located in exon 10 (coding exon 10) of the RPRD2 gene. This alteration results from a C to T substitution at nucleotide position 1496, causing the alanine (A) at amino acid position 499 to be replaced by a valine (V). 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	0.082
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	.;T
Eigen	Benign	0.015
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.52	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	.;N
MutationTaster	Benign	0.87	D;D;D
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.069
Sift	Uncertain	0.0020	D;D
Sift4G	Benign	0.12	T;T
Polyphen		0.65	P;P
Vest4		0.37
MutPred		0.18		.;Gain of sheet (P = 0.0266);
MVP		0.25
MPC		0.26
ClinPred		0.75	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-150437087;