Variant chr20-56468764-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016407.5(RTF2):c.67A>G(p.Lys23Glu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RTF2
NM_016407.5 missense, splice_region

Scores

Splicing: ADA: 0.6019

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.01

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RTF2	NM_016407.5 linkuse as main transcript	c.67A>G	p.Lys23Glu	missense_variant, splice_region_variant	1/9	ENST00000357348.10	NP_057491.2
RTF2	NM_001283035.2 linkuse as main transcript	c.67A>G	p.Lys23Glu	missense_variant, splice_region_variant	1/10		NP_001269964.1
RTF2	NM_001283036.2 linkuse as main transcript	c.67A>G	p.Lys23Glu	missense_variant, splice_region_variant	1/9		NP_001269965.1
RTF2	NM_001283037.2 linkuse as main transcript	c.67A>G	p.Lys23Glu	missense_variant, splice_region_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.67A>G	p.Lys23Glu	missense_variant, splice_region_variant	1/9	1	NM_016407.5	ENSP00000349906	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1426404

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

706484

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:

0.00

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

Sep 23, 2023

The c.67A>G (p.K23E) alteration is located in exon 1 (coding exon 1) of the RTFDC1 gene. This alteration results from a A to G substitution at nucleotide position 67, causing the lysine (K) at amino acid position 23 to be replaced by a glutamic acid (E). 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

Uncertain

0.50

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.097

.;.;T;T

Eigen

Uncertain

0.64

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.41

T;D;D;T

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.50

D;D;D;D

MetaSVM

Benign

-0.90

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.75

N;N;N;N

REVEL

Benign

0.22

Sift

Uncertain

0.014

D;T;D;T

Sift4G

Benign

0.098

T;D;T;D

Polyphen

0.85

.;.;P;.

Vest4

0.47

MutPred

0.51

Loss of MoRF binding (P = 0.0062);Loss of MoRF binding (P = 0.0062);Loss of MoRF binding (P = 0.0062);Loss of MoRF binding (P = 0.0062);

MVP

0.72

MPC

0.86

ClinPred

0.98

GERP RS

5.7

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.7

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.60

dbscSNV1_RF

Benign

0.43

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over