rs2270941

chr19-48935106-G-Achr19-48935106-G-T

Variant summary

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

The NM_014475.4(DHDH):c.197G>A(p.Ser66Asn) variant causes a missense change. The variant allele was found at a frequency of 0.269 in 1,562,794 control chromosomes in the GnomAD database, including 70,408 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.40 (15882 hom., cov: 33)
  • Exomes 𝑓: 0.25 (54526 hom.)
• Consequence: DHDH NM_014475.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.21

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1793906E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DHDH	NM_014475.4	c.197G>A	p.Ser66Asn	missense_variant	2/7	ENST00000221403.7
DHDH	XM_047438617.1	c.197G>A	p.Ser66Asn	missense_variant	2/5
DHDH	XM_005258748.5	c.25G>A	p.Ala9Thr	missense_variant	2/6
DHDH	XM_017026598.2	c.-53G>A		5_prime_UTR_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHDH	ENST00000221403.7	c.197G>A	p.Ser66Asn	missense_variant	2/7	1	NM_014475.4	P1
DHDH	ENST00000522614.5	c.197G>A	p.Ser66Asn	missense_variant	2/5	5
DHDH	ENST00000523250.5	c.197G>A	p.Ser66Asn	missense_variant	2/5	5
DHDH	ENST00000520557.1	c.161G>A	p.Ser54Asn	missense_variant, NMD_transcript_variant	2/5	5

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60955 AN: 151964 Hom.: 15833 Cov.: 33

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.365

GnomAD3 exomes AF: 0.338 AC: 60510 AN: 178820 Hom.: 12194 AF XY: 0.327 AC XY: 31433 AN XY: 96198

Gnomad AFR exome AF: 0.729

Gnomad AMR exome AF: 0.455

Gnomad ASJ exome AF: 0.227

Gnomad EAS exome AF: 0.515

Gnomad SAS exome AF: 0.403

Gnomad FIN exome AF: 0.344

Gnomad NFE exome AF: 0.214

Gnomad OTH exome AF: 0.286

GnomAD4 exome AF: 0.255 AC: 359511 AN: 1410712 Hom.: 54526 Cov.: 32 AF XY: 0.257 AC XY: 179119 AN XY: 697794

Gnomad4 AFR exome AF: 0.737

Gnomad4 AMR exome AF: 0.443

Gnomad4 ASJ exome AF: 0.228

Gnomad4 EAS exome AF: 0.528

Gnomad4 SAS exome AF: 0.400

Gnomad4 FIN exome AF: 0.335

Gnomad4 NFE exome AF: 0.210

Gnomad4 OTH exome AF: 0.291

GnomAD4 genome AF: 0.402 AC: 61074 AN: 152082 Hom.: 15882 Cov.: 33 AF XY: 0.408 AC XY: 30337 AN XY: 74350

Gnomad4 AFR AF: 0.724

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.534

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.368

Alfa AF: 0.249 Hom.: 13402

Bravo AF: 0.416

TwinsUK AF: 0.193 AC: 716

ALSPAC AF: 0.218 AC: 841

ESP6500AA AF: 0.702 AC: 3081

ESP6500EA AF: 0.215 AC: 1842

ExAC AF: 0.296 AC: 34862

Asia WGS AF: 0.499 AC: 1732 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
Cadd	Benign	18
Dann	Benign	0.93
DEOGEN2	Benign	0.0055	T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.15	T;T;T
MetaRNN	Benign	0.0000012	T;T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	1.5	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.55	T;D;T
Sift4G	Benign	0.40	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.046
MPC		0.12
ClinPred		0.0071	T
GERP RS		4.7
Varity_R		0.065
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2270941; hg19: chr19-49438363; COSMIC: COSV55482189;