NM_016940.3:c.47G>C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_016940.3(RWDD2B):​c.47G>C​(p.Ser16Thr) variant causes a missense 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RWDD2B NM_016940.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.101
• Publications: 0 publications found

Genes affected

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

LOC124905005 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -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 VariationId is 3436461.Status of the report is criteria_provided_single_submitter, 1 stars.

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.47G>C	p.Ser16Thr	missense	Exon 1 of 5	NP_058636.1	P57060
	RWDD2B	NM_001320724.2		c.-139G>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_001307653.1
	RWDD2B	NM_001320724.2		c.-139G>C		5_prime_UTR	Exon 1 of 6	NP_001307653.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RWDD2B	ENST00000493196.2	TSL:1 MANE Select	c.47G>C	p.Ser16Thr	missense	Exon 1 of 5	ENSP00000418693.1	P57060
	RWDD2B	ENST00000929248.1		c.47G>C	p.Ser16Thr	missense	Exon 1 of 5	ENSP00000599307.1
	RWDD2B	ENST00000286777.6	TSL:2	n.122G>C		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		0.10
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
PromoterAI		-0.0061	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.043
gMVP		0.15
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

hg19: chr21-30391552;