Variant 6-83196071-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000369724.5(RWDD2A):c.678C>A(p.Ser226Arg) 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 152,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Consequence

RWDD2A
ENST00000369724.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.268

Variant links:

Genes affected

RWDD2A (HGNC:21385): (RWD domain containing 2A)

RWDD2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.095207155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RWDD2A	NM_033411.5 linkuse as main transcript	c.678C>A	p.Ser226Arg	missense_variant	3/3	ENST00000369724.5	NP_219479.2	Q9UIY3-1B2R7R2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RWDD2A	ENST00000369724.5 linkuse as main transcript	c.678C>A	p.Ser226Arg	missense_variant	3/3	1	NM_033411.5	ENSP00000358739.3		Q9UIY3-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152110

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

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

250956

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135606

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000267

Hom.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

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

Oct 02, 2023

The c.678C>A (p.S226R) alteration is located in exon 3 (coding exon 2) of the RWDD2A gene. This alteration results from a C to A substitution at nucleotide position 678, causing the serine (S) at amino acid position 226 to be replaced by an arginine (R). 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

0.39

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.32

CADD

Benign

1.1

DANN

Benign

0.89

DEOGEN2

Benign

0.054

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.83

M_CAP

Benign

0.0048

MetaRNN

Benign

0.095

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.2

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.5

REVEL

Benign

0.23

Sift

Uncertain

0.0060

Sift4G

Benign

0.36

Polyphen

0.055

Vest4

0.23

MutPred

0.59

Loss of ubiquitination at K222 (P = 0.0536);

MVP

0.048

MPC

0.49

ClinPred

0.12

GERP RS

-3.1

Varity_R

0.25

gMVP

0.40

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