Genetic Variant NM_016940.3:c.169A>G (chr21-29008520-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016940.3(RWDD2B):c.169A>G(p.Ile57Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RWDD2B
NM_016940.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.01

Publications

1 publications found

Variant links:

Genes affected

RWDD2B (HGNC:1302): (RWD domain containing 2B)

RWDD2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06635067).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016940.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RWDD2B	NM_016940.3	MANE Select	c.169A>G	p.Ile57Val	missense	Exon 2 of 5	NP_058636.1	P57060
	RWDD2B	NM_001320724.2		c.82A>G	p.Ile28Val	missense	Exon 3 of 6	NP_001307653.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RWDD2B	ENST00000493196.2	TSL:1 MANE Select	c.169A>G	p.Ile57Val	missense	Exon 2 of 5	ENSP00000418693.1	P57060
RWDD2B	ENST00000929248.1		c.169A>G	p.Ile57Val	missense	Exon 2 of 5	ENSP00000599307.1
RWDD2B	ENST00000286777.6	TSL:2	n.244A>G		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251420

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461230

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726940

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111418

Other (OTH)

AF:

0.00

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.31

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.0014

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.54

M_CAP

Benign

0.0030

MetaRNN

Benign

0.066

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.42

PhyloP100

-1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

0.33

REVEL

Benign

0.010

Sift

Benign

0.84

Sift4G

Benign

0.36

Polyphen

0.0

Vest4

0.052

MutPred

0.36

Loss of catalytic residue at L62 (P = 0.0886)

MVP

0.37

MPC

0.16

ClinPred

0.064

GERP RS

-4.9

Varity_R

0.017

gMVP

0.11

Mutation Taster

=90/10

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over