Variant 20-4786234-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014737.3(RASSF2):c.908G>A(p.Arg303His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000051 in 1,606,462 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 2 hom. )

Consequence

RASSF2
NM_014737.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.52

Variant links:

Genes affected

RASSF2 (HGNC:9883): (Ras association domain family member 2) This gene encodes a protein that contains a Ras association domain. Similar to its cattle and sheep counterparts, this gene is located near the prion gene. Two alternatively spliced transcripts encoding the same isoform have been reported. [provided by RefSeq, Jul 2008]

RASSF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0563567).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASSF2	NM_014737.3 linkuse as main transcript	c.908G>A	p.Arg303His	missense_variant	11/12	ENST00000379400.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASSF2	ENST00000379400.8 linkuse as main transcript	c.908G>A	p.Arg303His	missense_variant	11/12	1	NM_014737.3	P1	P50749-1
RASSF2	ENST00000379376.2 linkuse as main transcript	c.908G>A	p.Arg303His	missense_variant	10/11	1		P1	P50749-1
RASSF2	ENST00000478553.1 linkuse as main transcript	n.878G>A		non_coding_transcript_exon_variant	8/9	1

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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

GnomAD3 exomes

AF:

0.000139

AC:

AN:

251458

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000358

AC:

AN:

1454160

Hom.:

Cov.:

AF XY:

0.0000359

AC XY:

AN XY:

723964

show subpopulations

Gnomad4 AFR exome

AF:

0.000481

Gnomad4 AMR exome

AF:

0.000649

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000362

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.000197

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000602

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000152

Hom.:

Bravo

AF:

0.000204

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Dec 07, 2021

The c.908G>A (p.R303H) alteration is located in exon 11 (coding exon 9) of the RASSF2 gene. This alteration results from a G to A substitution at nucleotide position 908, causing the arginine (R) at amino acid position 303 to be replaced by a histidine (H). 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

Benign

0.073

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.069

T;T

Eigen

Benign

0.073

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.90

M_CAP

Benign

0.0075

MetaRNN

Benign

0.056

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.059

Sift

Benign

0.12

T;T

Sift4G

Benign

0.098

T;T

Polyphen

0.55

P;P

Vest4

0.38

MVP

0.31

MPC

0.50

ClinPred

0.061

GERP RS

4.3

Varity_R

0.11

gMVP

0.33

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