Variant rs2071504 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_000937.5(POLR2A):c.2673C>T(p.Tyr891=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,367,392 control chromosomes in the GnomAD database, including 18,447 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.17 ( 2400 hom., cov: 32)

Exomes 𝑓: 0.16 ( 16047 hom. )

Consequence

POLR2A
NM_000937.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.955

Variant links:

Genes affected

POLR2A (HGNC:9187): (RNA polymerase II subunit A) This gene encodes the largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The product of this gene contains a carboxy terminal domain composed of heptapeptide repeats that are essential for polymerase activity. These repeats contain serine and threonine residues that are phosphorylated in actively transcribing RNA polymerase. In addition, this subunit, in combination with several other polymerase subunits, forms the DNA binding domain of the polymerase, a groove in which the DNA template is transcribed into RNA. [provided by RefSeq, Jul 2008]

POLR2A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 17-7502618-C-T is Benign according to our data. Variant chr17-7502618-C-T is described in ClinVar as [Benign]. Clinvar id is 3056621.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.955 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR2A	NM_000937.5 linkuse as main transcript	c.2673C>T	p.Tyr891=	synonymous_variant	16/30	ENST00000643490.2	NP_000928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	Appris
POLR2A	ENST00000674977.2 linkuse as main transcript	c.2673C>T	p.Tyr891=	synonymous_variant	16/30		ENSP00000502190	P1
POLR2A	ENST00000617998.6 linkuse as main transcript	n.3072C>T		non_coding_transcript_exon_variant	16/29	1
POLR2A	ENST00000576114.1 linkuse as main transcript	n.139C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

25210

AN:

152074

Hom.:

2384

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.141

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.0960

Gnomad EAS

AF:

0.206

Gnomad SAS

AF:

0.204

Gnomad FIN

AF:

0.311

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.152

Gnomad OTH

AF:

0.150

GnomAD3 exomes

AF:

0.182

AC:

45669

AN:

251344

Hom.:

4602

AF XY:

0.179

AC XY:

24375

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.133

Gnomad AMR exome

AF:

0.216

Gnomad ASJ exome

AF:

0.0964

Gnomad EAS exome

AF:

0.202

Gnomad SAS exome

AF:

0.211

Gnomad FIN exome

AF:

0.308

Gnomad NFE exome

AF:

0.151

Gnomad OTH exome

AF:

0.174

GnomAD4 exome

AF:

0.157

AC:

191051

AN:

1215198

Hom.:

16047

Cov.:

AF XY:

0.158

AC XY:

95438

AN XY:

602260

show subpopulations

Gnomad4 AFR exome

AF:

0.128

Gnomad4 AMR exome

AF:

0.218

Gnomad4 ASJ exome

AF:

0.0938

Gnomad4 EAS exome

AF:

0.206

Gnomad4 SAS exome

AF:

0.206

Gnomad4 FIN exome

AF:

0.300

Gnomad4 NFE exome

AF:

0.147

Gnomad4 OTH exome

AF:

0.160

GnomAD4 genome

AF:

0.166

AC:

25243

AN:

152194

Hom.:

2400

Cov.:

AF XY:

0.175

AC XY:

12985

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.138

Gnomad4 AMR

AF:

0.198

Gnomad4 ASJ

AF:

0.0960

Gnomad4 EAS

AF:

0.206

Gnomad4 SAS

AF:

0.205

Gnomad4 FIN

AF:

0.311

Gnomad4 NFE

AF:

0.152

Gnomad4 OTH

AF:

0.157

Alfa

AF:

0.152

Hom.:

1390

Bravo

AF:

0.154

Asia WGS

AF:

0.266

AC:

924

AN:

3478

EpiCase

AF:

0.130

EpiControl

AF:

0.133

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

POLR2A-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 06, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.23

DANN

Benign

0.70

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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