Variant X-17800602-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_021785.6(RAI2):c.1409G>C(p.Arg470Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000126 in 1,209,875 control chromosomes in the GnomAD database, including 2 homozygotes. There are 37 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 1 hom., 9 hem., cov: 23)

Exomes 𝑓: 0.000099 ( 1 hom. 28 hem. )

Consequence

RAI2
NM_021785.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.46

Variant links:

Genes affected

RAI2 (HGNC:9835): (retinoic acid induced 2) Retinoic acid plays a critical role in development, cellular growth, and differentiation. The specific function of this retinoic acid-induced gene has not yet been determined but it may play a role in development. The chromosomal location of this gene designates it to be a candidate for diseases such as Nance-Horan syndrome, sensorineural deafness, non-specific X-linked cognitive disability, oral-facial-digital syndrome, and Fried syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

RAI2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2635985).

BS2

High Hemizygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAI2	NM_021785.6 linkuse as main transcript	c.1409G>C	p.Arg470Thr	missense_variant	2/2	ENST00000451717.6	NP_068557.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAI2	ENST00000451717.6 linkuse as main transcript	c.1409G>C	p.Arg470Thr	missense_variant	2/2	1	NM_021785.6	ENSP00000401323	P1	Q9Y5P3-1

Frequencies

GnomAD3 genomes

AF:

0.000394

AC:

AN:

111779

Hom.:

Cov.:

AF XY:

0.000265

AC XY:

AN XY:

33947

show subpopulations

Gnomad AFR

AF:

0.000978

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000189

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00140

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00400

GnomAD3 exomes

AF:

0.000180

AC:

AN:

183387

Hom.:

AF XY:

0.0000885

AC XY:

AN XY:

67829

show subpopulations

Gnomad AFR exome

AF:

0.00144

Gnomad AMR exome

AF:

0.0000730

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000577

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000884

GnomAD4 exome

AF:

0.0000993

AC:

109

AN:

1098043

Hom.:

Cov.:

AF XY:

0.0000770

AC XY:

AN XY:

363403

show subpopulations

Gnomad4 AFR exome

AF:

0.000644

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000728

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.00148

GnomAD4 genome

AF:

0.000393

AC:

AN:

111832

Hom.:

Cov.:

AF XY:

0.000265

AC XY:

AN XY:

34010

show subpopulations

Gnomad4 AFR

AF:

0.000976

Gnomad4 AMR

AF:

0.000189

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00141

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00395

Alfa

AF:

0.000304

Hom.:

Bravo

AF:

0.000325

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000189

AC:

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 04, 2023

The c.1409G>C (p.R470T) alteration is located in exon 3 (coding exon 1) of the RAI2 gene. This alteration results from a G to C substitution at nucleotide position 1409, causing the arginine (R) at amino acid position 470 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

Benign

0.29

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Uncertain

0.060

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.25

.;T;T;T;T

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.77

T;.;.;.;T

M_CAP

Pathogenic

0.43

MetaRNN

Benign

0.26

T;T;T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Benign

0.90

.;L;L;L;L

MutationTaster

Benign

0.66

D;D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-5.1

D;D;D;D;D

REVEL

Benign

0.27

Sift

Pathogenic

0.0

D;D;D;D;D

Sift4G

Uncertain

0.032

D;T;T;T;T

Polyphen

1.0

.;D;D;D;D

Vest4

0.79

MVP

0.93

MPC

0.20

ClinPred

0.096

GERP RS

5.1

Varity_R

0.88

gMVP

0.45

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