chr21-29007845-G-C

Variant names:

• chr21-29007845-G-C
• rs781218634
• NM_016940.3:c.641C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016940.3(RWDD2B):​c.641C>G​(p.Ser214Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S214F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RWDD2B NM_016940.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.05
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.641C>G	p.Ser214Cys	missense	Exon 4 of 5	NP_058636.1	P57060
	RWDD2B	NM_001320724.2		c.554C>G	p.Ser185Cys	missense	Exon 5 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.641C>G	p.Ser214Cys	missense	Exon 4 of 5	ENSP00000418693.1	P57060
	RWDD2B	ENST00000929248.1		c.671C>G	p.Ser224Cys	missense	Exon 4 of 5	ENSP00000599307.1
	RWDD2B	ENST00000286777.6	TSL:2	n.648C>G		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.080	T
Eigen	Benign	0.040
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0056	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.1
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.097
Sift	Benign	0.087	T
Sift4G	Benign	0.083	T
Polyphen		0.97	D
Vest4		0.31
MutPred		0.53		Loss of disorder (P = 0.0052)
MVP		0.58
MPC		0.25
ClinPred		0.63	D
GERP RS		4.8
Varity_R		0.085
gMVP		0.40
Mutation Taster		=78/22	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

dbSNP: rs781218634; hg19: chr21-30380166;