rs1441940716

Variant names:

• chr21-29007939-C-G
• rs1441940716
• NM_016940.3:c.547G>C

Your query was ambiguous. Multiple possible variants found:

• chr21-29007939-C-G
• chr21-29007939-C-T

Variant summary

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

The NM_016940.3(RWDD2B):​c.547G>C​(p.Val183Leu) 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 152,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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. V183I) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: RWDD2B NM_016940.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058862925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RWDD2B	NM_016940.3	c.547G>C	p.Val183Leu	missense_variant	Exon 4 of 5	ENST00000493196.2	NP_058636.1
RWDD2B	NM_001320724.2	c.460G>C	p.Val154Leu	missense_variant	Exon 5 of 6		NP_001307653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RWDD2B	ENST00000493196.2	c.547G>C	p.Val183Leu	missense_variant	Exon 4 of 5	1	NM_016940.3	ENSP00000418693.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152240 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152240 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74374

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

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

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.0
DANN	Benign	0.71
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.026
Sift	Benign	0.19	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.074
MutPred		0.36		Gain of relative solvent accessibility (P = 0.1259);
MVP		0.12
MPC		0.20
ClinPred		0.031	T
GERP RS		1.3
Varity_R		0.046
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs1441940716; hg19: chr21-30380260;