chr21-29018988-A-G

Variant names:

• chr21-29018988-A-G
• rs878797
• NM_016940.3:c.67+223T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

Genes affected

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

LOC124905005 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RWDD2B	NM_016940.3	MANE Select	c.67+223T>C		intron	N/A	NP_058636.1
	RWDD2B	NM_001320724.2		c.-119+223T>C		intron	N/A	NP_001307653.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RWDD2B	ENST00000493196.2	TSL:1 MANE Select	c.67+223T>C		intron	N/A	ENSP00000418693.1
	RWDD2B	ENST00000286777.6	TSL:2	n.142+223T>C		intron	N/A
	RWDD2B	ENST00000466746.1	TSL:2	n.96+223T>C		intron	N/A

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

African (AFR) AF: 0.551 AC: 22841 AN: 41486

American (AMR) AF: 0.608 AC: 9285 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 2463 AN: 3466

East Asian (EAS) AF: 0.491 AC: 2525 AN: 5146

South Asian (SAS) AF: 0.778 AC: 3754 AN: 4826

European-Finnish (FIN) AF: 0.830 AC: 8782 AN: 10576

Middle Eastern (MID) AF: 0.555 AC: 162 AN: 292

European-Non Finnish (NFE) AF: 0.739 AC: 50194 AN: 67964

Other (OTH) AF: 0.662 AC: 1399 AN: 2114

Alfa AF: 0.697 Hom.: 4902

Bravo AF: 0.647

Asia WGS AF: 0.632 AC: 2199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.61
DANN	Benign	0.55
PhyloP100		-0.22
PromoterAI		-0.024	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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