rs756844857

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016407.5(RTF2):c.884C>A(p.Ser295Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S295F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

RTF2
NM_016407.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.13

Publications

0 publications found

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:

GCNT7 (HGNC:16099): (glucosaminyl (N-acetyl) transferase family member 7) Predicted to enable acetylglucosaminyltransferase activity. Predicted to be involved in protein glycosylation. Predicted to be located in Golgi membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

GCNT7 links:

FAM209A (HGNC:16100): (family with sequence similarity 209 member A) Located in extracellular exosome and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FAM209A links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1549856).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016407.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RTF2	NM_016407.5	MANE Select	c.884C>A	p.Ser295Tyr	missense	Exon 9 of 9	NP_057491.2	Q9BY42
RTF2	NM_001283035.2		c.974C>A	p.Ser325Tyr	missense	Exon 10 of 10	NP_001269964.1	A0A0A0MQR2
RTF2	NM_001283036.2		c.881C>A	p.Ser294Tyr	missense	Exon 9 of 9	NP_001269965.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RTF2	ENST00000357348.10	TSL:1 MANE Select	c.884C>A	p.Ser295Tyr	missense	Exon 9 of 9	ENSP00000349906.6	Q9BY42
GCNT7	ENST00000243913.8	TSL:2	c.-929-3923G>T		intron	N/A	ENSP00000243913.4	Q6ZNI0
RTF2	ENST00000477573.1	TSL:1	n.1534C>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152234

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74370

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000241

AC:

AN:

41462

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.026

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0098

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

PhyloP100

2.1

PrimateAI

Uncertain

0.60

REVEL

Benign

0.14

Sift4G

Uncertain

0.043

Vest4

0.34

MutPred

0.28

Loss of disorder (P = 0.0011)

MVP

0.64

MPC

0.61

ClinPred

0.86

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.20

Mutation Taster

=76/24

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over