dbSNP rs606231342: POLR2F:c.453-24860G>A (chr22-38016208-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2PP5BP4

The NM_001301130.2(POLR2F):c.453-24860G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Consequence

POLR2F
NM_001301130.2 intron

Scores

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 0.209

Publications

0 publications found

Variant links:

Genes affected

POLR2F (HGNC:9193): (RNA polymerase II, I and III subunit F) This gene encodes the sixth largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. In yeast, this polymerase subunit, in combination with at least two other subunits, forms a structure that stabilizes the transcribing polymerase on the DNA template. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

POLR2F links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 22-38016208-G-A is Pathogenic according to our data. Variant chr22-38016208-G-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 156720.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
POLR2F	NM_001301130.2 link	c.453-24860G>A	intron_variant	Intron 5 of 5	NP_001288059.1
POLR2F	NM_001363825.1 link	c.*39-24860G>A	intron_variant	Intron 5 of 5	NP_001350754.1
POLR2F	NM_001301131.2 link	c.294-24860G>A	intron_variant	Intron 4 of 4	NP_001288060.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
POLR2F	ENST00000407936.5 link	c.453-24860G>A	intron_variant	Intron 5 of 5	3	ENSP00000385725.1
POLR2F	ENST00000333418.4 link	c.120-9661G>A	intron_variant	Intron 1 of 2	2	ENSP00000332130.4
POLR2F	ENST00000405557.5 link	c.294-9371G>A	intron_variant	Intron 4 of 4	5	ENSP00000384112.1
POLR2F	ENST00000427034.1 link	c.113-9661G>A	intron_variant	Intron 1 of 1	2	ENSP00000389307.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41438

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000340

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Hirschsprung disease, susceptibility to, 1

Pathogenic:1

Dec 11, 2013

U955 Equipe 11, INSERM

Significance:Likely pathogenic

Review Status:no assertion criteria provided

Collection Method:in vitro

Regulation of SOX10 expression -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

6.1

(source)

DANN

Benign

0.63

PhyloP100

0.21

Mutation Taster

=41/59

disease causing (ClinVar)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over