rs878797

Positions:

• chr21-29018988-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016940.3(RWDD2B):​c.67+223T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 152,050 control chromosomes in the GnomAD database, including 35,152 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.67 (35152 hom., cov: 32)
• Consequence: RWDD2B NM_016940.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216

Genes affected

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

LOC124905005 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RWDD2B	NM_016940.3	c.67+223T>C		intron_variant		ENST00000493196.2	NP_058636.1
LOC124905005	XR_007067836.1	n.738A>G		non_coding_transcript_exon_variant	2/2
RWDD2B	NM_001320724.2	c.-119+223T>C		intron_variant			NP_001307653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RWDD2B	ENST00000493196.2	c.67+223T>C		intron_variant		1	NM_016940.3	ENSP00000418693	P1

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102071 AN: 151932 Hom.: 35130 Cov.: 32

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.663

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.672 AC: 102148 AN: 152050 Hom.: 35152 Cov.: 32 AF XY: 0.677 AC XY: 50298 AN XY: 74330

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.711

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.778

Gnomad4 FIN AF: 0.830

Gnomad4 NFE AF: 0.739

Gnomad4 OTH AF: 0.662

Alfa AF: 0.703 Hom.: 4787

Bravo AF: 0.647

Asia WGS AF: 0.632 AC: 2199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.61
DANN	Benign	0.55

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

LitVar

Other links and lift over

dbSNP: rs878797; hg19: chr21-30391309; COSMIC: COSV54502267;