rs2270939

chr19-48939676-T-Cchr19-48939676-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014475.4(DHDH):c.594T>C(p.Ser198=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,603,172 control chromosomes in the GnomAD database, including 53,048 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 0.34 (11900 hom., cov: 31)
  • Exomes 𝑓: 0.21 (41148 hom.)
• Consequence: DHDH NM_014475.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63

Genes affected

DHDH (HGNC:17887): (dihydrodiol dehydrogenase) This gene encodes an enzyme that belongs to the family of dihydrodiol dehydrogenases, which exist in multiple forms in mammalian tissues and are involved in the metabolism of xenobiotics and sugars. These enzymes catalyze the NADP1-linked oxidation of transdihydrodiols of aromatic hydrocarbons to corresponding catechols. This enzyme is a dimeric dihydrodiol dehydrogenase, and it differs from monomeric dihydrodiol dehydrogenases in its high substrate specificity for trans-dihydrodiols of aromatic hydrocarbons in the oxidative direction. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP7: Synonymous conserved (PhyloP=-2.63 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DHDH	NM_014475.4	c.594T>C	p.Ser198=	synonymous_variant	4/7	ENST00000221403.7
DHDH	XM_017026598.2	c.345T>C	p.Ser115=	synonymous_variant	4/7
DHDH	XM_047438617.1	c.594T>C	p.Ser198=	synonymous_variant	4/5
DHDH	XM_005258748.5	c.258T>C	p.Ser86=	synonymous_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHDH	ENST00000221403.7	c.594T>C	p.Ser198=	synonymous_variant	4/7	1	NM_014475.4	P1
DHDH	ENST00000522614.5	c.594T>C	p.Ser198=	synonymous_variant	4/5	5
DHDH	ENST00000523250.5	c.203-2764T>C		intron_variant		5
DHDH	ENST00000520557.1	c.394T>C	p.Cys132Arg	missense_variant, NMD_transcript_variant	3/5	5

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51593 AN: 151890 Hom.: 11852 Cov.: 31

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.301

GnomAD3 exomes AF: 0.281 AC: 70016 AN: 249440 Hom.: 12685 AF XY: 0.272 AC XY: 36707 AN XY: 134906

Gnomad AFR exome AF: 0.646

Gnomad AMR exome AF: 0.273

Gnomad ASJ exome AF: 0.187

Gnomad EAS exome AF: 0.556

Gnomad SAS exome AF: 0.349

Gnomad FIN exome AF: 0.314

Gnomad NFE exome AF: 0.172

Gnomad OTH exome AF: 0.235

GnomAD4 exome AF: 0.212 AC: 307976 AN: 1451164 Hom.: 41148 Cov.: 32 AF XY: 0.214 AC XY: 153967 AN XY: 719718

Gnomad4 AFR exome AF: 0.653

Gnomad4 AMR exome AF: 0.274

Gnomad4 ASJ exome AF: 0.186

Gnomad4 EAS exome AF: 0.551

Gnomad4 SAS exome AF: 0.348

Gnomad4 FIN exome AF: 0.306

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome AF: 0.340 AC: 51704 AN: 152008 Hom.: 11900 Cov.: 31 AF XY: 0.346 AC XY: 25728 AN XY: 74302

Gnomad4 AFR AF: 0.637

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.305

Alfa AF: 0.198 Hom.: 5186

Bravo AF: 0.348

Asia WGS AF: 0.478 AC: 1660 AN: 3478

EpiCase AF: 0.171

EpiControl AF: 0.164

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.045
Dann	Benign	0.25

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: rs2270939; hg19: chr19-49442933; COSMIC: COSV55481591;