rs2270941

Variant names:

• chr19-48935106-G-A
• rs2270941
• NM_014475.4:c.197G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-48935106-G-A
• chr19-48935106-G-C
• chr19-48935106-G-T

Variant summary

Our verdict is Benign. The variant received -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. 13/20 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. S66R) has been classified as Uncertain significance.

• 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
• Publications: 31 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DHDH	NM_014475.4	c.197G>A	p.Ser66Asn	missense_variant	Exon 2 of 7	ENST00000221403.7	NP_055290.1
DHDH	XM_047438617.1	c.197G>A	p.Ser66Asn	missense_variant	Exon 2 of 5		XP_047294573.1
DHDH	XM_005258748.5	c.25G>A	p.Ala9Thr	missense_variant	Exon 2 of 6		XP_005258805.1
DHDH	XM_017026598.2	c.-53G>A		5_prime_UTR_variant	Exon 2 of 7		XP_016882087.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHDH	ENST00000221403.7	c.197G>A	p.Ser66Asn	missense_variant	Exon 2 of 7	1	NM_014475.4	ENSP00000221403.2
DHDH	ENST00000522614.5	c.197G>A	p.Ser66Asn	missense_variant	Exon 2 of 5	5		ENSP00000428672.1
DHDH	ENST00000523250.5	c.197G>A	p.Ser66Asn	missense_variant	Exon 2 of 5	5		ENSP00000428935.1
DHDH	ENST00000520557.1	n.161G>A		non_coding_transcript_exon_variant	Exon 2 of 5	5		ENSP00000430360.1

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

GnomAD2 exomes AF: 0.338 AC: 60510 AN: 178820 AF XY: 0.327

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 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

African (AFR) AF: 0.737 AC: 23776 AN: 32268

American (AMR) AF: 0.443 AC: 16647 AN: 37588

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 5774 AN: 25380

East Asian (EAS) AF: 0.528 AC: 19514 AN: 36976

South Asian (SAS) AF: 0.400 AC: 31344 AN: 78302

European-Finnish (FIN) AF: 0.335 AC: 15628 AN: 46662

Middle Eastern (MID) AF: 0.273 AC: 1545 AN: 5664

European-Non Finnish (NFE) AF: 0.210 AC: 228243 AN: 1089244

Other (OTH) AF: 0.291 AC: 17040 AN: 58628

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

African (AFR) AF: 0.724 AC: 30032 AN: 41496

American (AMR) AF: 0.385 AC: 5881 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 833 AN: 3470

East Asian (EAS) AF: 0.534 AC: 2756 AN: 5164

South Asian (SAS) AF: 0.424 AC: 2045 AN: 4818

European-Finnish (FIN) AF: 0.356 AC: 3762 AN: 10576

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14690 AN: 67978

Other (OTH) AF: 0.368 AC: 777 AN: 2112

Alfa AF: 0.272 Hom.: 35606

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
PhyloP100		5.2
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
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2270941; hg19: chr19-49438363; COSMIC: COSV55482189;