21-29019231-C-G

Variant names:

• chr21-29019231-C-G
• NM_016940.3:c.47G>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001320724.2(RWDD2B):​c.-139G>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RWDD2B NM_001320724.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.101

Genes affected

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

LOC124905005 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040411532).
• BP6: Variant 21-29019231-C-G is Benign according to our data. Variant chr21-29019231-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3436461.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RWDD2B	NM_016940.3	c.47G>C	p.Ser16Thr	missense_variant	Exon 1 of 5	ENST00000493196.2	NP_058636.1
RWDD2B	NM_001320724.2	c.-139G>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6		NP_001307653.1
RWDD2B	NM_001320724.2	c.-139G>C		5_prime_UTR_variant	Exon 1 of 6		NP_001307653.1
LOC124905005	XR_007067836.1	n.981C>G		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RWDD2B	ENST00000493196.2	c.47G>C	p.Ser16Thr	missense_variant	Exon 1 of 5	1	NM_016940.3	ENSP00000418693.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Nov 10, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	3.4
DANN	Benign	0.79
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.011
Sift	Benign	0.60	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.12		Gain of catalytic residue at S16 (P = 0.0225);
MVP		0.072
MPC		0.18
ClinPred		0.066	T
GERP RS		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.043
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-30391552;