chr6-116592949-ATT-A

Variant names:

• chr6-116592949-ATT-A
• rs2243350
• NM_015952.4:c.611-17_611-16delTT

Variant summary

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

The NM_015952.4(RWDD1):​c.611-17_611-16delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00422 in 1,393,576 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0047 (0 hom.)
• Consequence: RWDD1 NM_015952.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680
• Publications: 2 publications found

Genes affected

RWDD1 (HGNC:20993): (RWD domain containing 1) Predicted to be involved in several processes, including cellular response to lipid; cytoplasmic translation; and positive regulation of androgen receptor activity. Predicted to be located in cytoplasm. Predicted to be part of polysome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• PM2: Variant has high frequency in the SAS (0.00848) population. However there is too low homozygotes in high coverage region: (expected more than 6, got 0).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015952.4. 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
	RWDD1	NM_015952.4	MANE Select	c.611-17_611-16delTT		intron	N/A	NP_057036.2
	RWDD1	NM_001007464.3		c.323-17_323-16delTT		intron	N/A	NP_001007465.1
	RWDD1	NM_016104.4		c.323-17_323-16delTT		intron	N/A	NP_057188.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RWDD1	ENST00000466444.7	TSL:1 MANE Select	c.611-30_611-29delTT		intron	N/A	ENSP00000420357.2
	RWDD1	ENST00000487832.6	TSL:1	c.323-30_323-29delTT		intron	N/A	ENSP00000428778.1

Frequencies

GnomAD3 genomes AF: 0.0000987 AC: 14 AN: 141902 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000258

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000703

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000811

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000774

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0108 AC: 1581 AN: 145910 AF XY: 0.0108

Gnomad AFR exome AF: 0.00737

Gnomad AMR exome AF: 0.00978

Gnomad ASJ exome AF: 0.0155

Gnomad EAS exome AF: 0.0104

Gnomad FIN exome AF: 0.0133

Gnomad NFE exome AF: 0.0101

Gnomad OTH exome AF: 0.0127

GnomAD4 exome AF: 0.00469 AC: 5865 AN: 1251626 Hom.: 0 AF XY: 0.00488 AC XY: 3052 AN XY: 624816

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00530 AC: 149 AN: 28112

American (AMR) AF: 0.00842 AC: 291 AN: 34560

Ashkenazi Jewish (ASJ) AF: 0.00873 AC: 193 AN: 22104

East Asian (EAS) AF: 0.00683 AC: 239 AN: 35004

South Asian (SAS) AF: 0.00906 AC: 654 AN: 72190

European-Finnish (FIN) AF: 0.00839 AC: 358 AN: 42662

Middle Eastern (MID) AF: 0.00561 AC: 26 AN: 4632

European-Non Finnish (NFE) AF: 0.00384 AC: 3686 AN: 960378

Other (OTH) AF: 0.00517 AC: 269 AN: 51984

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000986 AC: 14 AN: 141950 Hom.: 0 Cov.: 29 AF XY: 0.0000727 AC XY: 5 AN XY: 68798

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000258 AC: 1 AN: 38820

American (AMR) AF: 0.0000702 AC: 1 AN: 14238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3340

East Asian (EAS) AF: 0.00 AC: 0 AN: 4856

South Asian (SAS) AF: 0.00 AC: 0 AN: 4420

European-Finnish (FIN) AF: 0.000811 AC: 7 AN: 8636

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.0000775 AC: 5 AN: 64554

Other (OTH) AF: 0.00 AC: 0 AN: 1946

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0127 Hom.: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.068
Mutation Taster		=100/0	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: rs2243350; hg19: chr6-116914112;