6-83193914-T-TG

Position:

• chr6-83193914-T-TG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_033411.5(RWDD2A):​c.-140-389dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 149,628 control chromosomes in the GnomAD database, including 3,451 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3448 hom., cov: 24)
  • Exomes 𝑓: 0.11 (3 hom.)
• Consequence: RWDD2A NM_033411.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.239

Genes affected

RWDD2A (HGNC:21385): (RWD domain containing 2A)

PGM3 (HGNC:8907): (phosphoglucomutase 3) This gene encodes a member of the phosphohexose mutase family. The encoded protein mediates both glycogen formation and utilization by catalyzing the interconversion of glucose-1-phosphate and glucose-6-phosphate. A non-synonymous single nucleotide polymorphism in this gene may play a role in resistance to diabetic nephropathy and neuropathy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 6-83193914-T-TG is Benign according to our data. Variant chr6-83193914-T-TG is described in ClinVar as [Benign]. Clinvar id is 1275110.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RWDD2A	NM_033411.5	c.-140-389dup		intron_variant		ENST00000369724.5	NP_219479.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RWDD2A	ENST00000369724.5	c.-140-389dup		intron_variant		1	NM_033411.5	ENSP00000358739	P1
PGM3	ENST00000507554.2	c.-95_-94insC		5_prime_UTR_variant	1/13	4		ENSP00000425558	P1
PGM3	ENST00000506587.5			upstream_gene_variant		2		ENSP00000425809

Frequencies

GnomAD3 genomes AF: 0.213 AC: 31577 AN: 148380 Hom.: 3449 Cov.: 24

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.0794

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.110 AC: 125 AN: 1136 Hom.: 3 Cov.: 0 AF XY: 0.118 AC XY: 77 AN XY: 652

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0815

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.100

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.213 AC: 31599 AN: 148492 Hom.: 3448 Cov.: 24 AF XY: 0.215 AC XY: 15563 AN XY: 72382

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.210

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 28, 2020

- -

Computational scores

Source: dbNSFP v4.3

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: rs16885957; hg19: chr6-83903633;