Variant 20-56468722-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_016407.5(RTF2):c.25C>A(p.Pro9Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000696 in 1,437,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

RTF2
NM_016407.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.79

Variant links:

Genes affected

RTF2 (HGNC:15890): (replication termination factor 2) Enables DNA binding activity. Involved in cellular response to hydroxyurea and regulation of DNA stability. Located in replication fork. [provided by Alliance of Genome Resources, Apr 2022]

RTF2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.963

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RTF2	NM_016407.5 linkuse as main transcript	c.25C>A	p.Pro9Thr	missense_variant	1/9	ENST00000357348.10	NP_057491.2
RTF2	NM_001283035.2 linkuse as main transcript	c.25C>A	p.Pro9Thr	missense_variant	1/10		NP_001269964.1
RTF2	NM_001283036.2 linkuse as main transcript	c.25C>A	p.Pro9Thr	missense_variant	1/9		NP_001269965.1
RTF2	NM_001283037.2 linkuse as main transcript	c.25C>A	p.Pro9Thr	missense_variant	1/8		NP_001269966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTF2	ENST00000357348.10 linkuse as main transcript	c.25C>A	p.Pro9Thr	missense_variant	1/9	1	NM_016407.5	ENSP00000349906	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.96e-7

AC:

AN:

1437066

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

712540

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:

0.0000121

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 13, 2021

The c.25C>A (p.P9T) alteration is located in exon 1 (coding exon 1) of the RTFDC1 gene. This alteration results from a C to A substitution at nucleotide position 25, causing the proline (P) at amino acid position 9 to be replaced by a threonine (T). 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

0.99

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.21

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

.;.;T;T

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.89

FATHMM_MKL

Benign

0.43

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Benign

0.056

MetaRNN

Pathogenic

0.96

D;D;D;D

MetaSVM

Uncertain

-0.27

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-7.4

D;D;D;D

REVEL

Uncertain

0.63

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

.;.;D;.

Vest4

0.79

MutPred

0.88

Gain of phosphorylation at P9 (P = 0.0205);Gain of phosphorylation at P9 (P = 0.0205);Gain of phosphorylation at P9 (P = 0.0205);Gain of phosphorylation at P9 (P = 0.0205);

MVP

0.78

MPC

0.96

ClinPred

1.0

GERP RS

5.7

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

gMVP

0.66

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