10-12089082-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018706.7(DHTKD1):c.814T>G(p.Tyr272Asp) variant causes a missense change. The variant allele was found at a frequency of 0.574 in 1,613,602 control chromosomes in the GnomAD database, including 272,936 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 19735 hom., cov: 32)

Exomes 𝑓: 0.58 ( 253201 hom. )

Consequence

DHTKD1
NM_018706.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 6.83

Publications

37 publications found

Variant links:

Genes affected

DHTKD1 (HGNC:23537): (dehydrogenase E1 and transketolase domain containing 1) This gene encodes a component of a mitochondrial 2-oxoglutarate-dehydrogenase-complex-like protein involved in the degradation pathways of several amino acids, including lysine. Mutations in this gene are associated with 2-aminoadipic 2-oxoadipic aciduria and Charcot-Marie-Tooth Disease Type 2Q. [provided by RefSeq, May 2013]

DHTKD1 Gene-Disease associations (from GenCC):

2-aminoadipic 2-oxoadipic aciduria
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
Charcot-Marie-Tooth disease axonal type 2Q
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

DHTKD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.3552481E-6).

BP6

Variant 10-12089082-T-G is Benign according to our data. Variant chr10-12089082-T-G is described in ClinVar as Benign. ClinVar VariationId is 1168372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHTKD1	NM_018706.7 link	c.814T>G	p.Tyr272Asp	missense_variant	Exon 5 of 17	ENST00000263035.9	NP_061176.4	Q96HY7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DHTKD1	ENST00000263035.9 link	c.814T>G	p.Tyr272Asp	missense_variant	Exon 5 of 17	1	NM_018706.7	ENSP00000263035.4	Q96HY7
DHTKD1	ENST00000437298.1 link	c.619T>G	p.Tyr207Asp	missense_variant	Exon 4 of 5	3		ENSP00000388163.1	C9JWN1
DHTKD1	ENST00000465617.1 link	n.299+1353T>G		intron_variant	Intron 2 of 3	3
DHTKD1	ENST00000415935.1 link	c.-93T>G		upstream_gene_variant		2		ENSP00000400625.1	H7C1J3

Frequencies

GnomAD3 genomes

AF:

0.486

AC:

73815

AN:

151838

Hom.:

19729

Cov.:

show subpopulations

Gnomad AFR

AF:

0.258

Gnomad AMI

AF:

0.615

Gnomad AMR

AF:

0.539

Gnomad ASJ

AF:

0.650

Gnomad EAS

AF:

0.467

Gnomad SAS

AF:

0.720

Gnomad FIN

AF:

0.471

Gnomad MID

AF:

0.658

Gnomad NFE

AF:

0.588

Gnomad OTH

AF:

0.519

GnomAD2 exomes

AF:

0.556

AC:

139871

AN:

251450

AF XY:

0.574

show subpopulations

Gnomad AFR exome

AF:

0.249

Gnomad AMR exome

AF:

0.492

Gnomad ASJ exome

AF:

0.650

Gnomad EAS exome

AF:

0.456

Gnomad FIN exome

AF:

0.469

Gnomad NFE exome

AF:

0.598

Gnomad OTH exome

AF:

0.572

GnomAD4 exome

AF:

0.584

AC:

853015

AN:

1461646

Hom.:

253201

Cov.:

AF XY:

0.590

AC XY:

428669

AN XY:

727152

show subpopulations

African (AFR)

AF:

0.246

AC:

8224

AN:

33470

American (AMR)

AF:

0.495

AC:

22121

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.657

AC:

17160

AN:

26132

East Asian (EAS)

AF:

0.492

AC:

19546

AN:

39698

South Asian (SAS)

AF:

0.719

AC:

62020

AN:

86250

European-Finnish (FIN)

AF:

0.483

AC:

25800

AN:

53416

Middle Eastern (MID)

AF:

0.637

AC:

3675

AN:

5766

European-Non Finnish (NFE)

AF:

0.594

AC:

660217

AN:

1111800

Other (OTH)

AF:

0.567

AC:

34252

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

20324

40649

60973

81298

101622

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17952

35904

53856

71808

89760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.486

AC:

73834

AN:

151956

Hom.:

19735

Cov.:

AF XY:

0.487

AC XY:

36183

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.258

AC:

10679

AN:

41450

American (AMR)

AF:

0.538

AC:

8188

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.650

AC:

2256

AN:

3470

East Asian (EAS)

AF:

0.467

AC:

2410

AN:

5162

South Asian (SAS)

AF:

0.720

AC:

3473

AN:

4824

European-Finnish (FIN)

AF:

0.471

AC:

4973

AN:

10554

Middle Eastern (MID)

AF:

0.660

AC:

194

AN:

294

European-Non Finnish (NFE)

AF:

0.588

AC:

39999

AN:

67972

Other (OTH)

AF:

0.524

AC:

1104

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1785

3570

5356

7141

8926

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

672

1344

2016

2688

3360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.567

Hom.:

110795

Bravo

AF:

0.475

TwinsUK

AF:

0.607

AC:

2252

ALSPAC

AF:

0.591

AC:

2278

ESP6500AA

AF:

0.268

AC:

1180

ESP6500EA

AF:

0.589

AC:

5064

ExAC

AF:

0.559

AC:

67912

Asia WGS

AF:

0.612

AC:

2126

AN:

3478

EpiCase

AF:

0.611

EpiControl

AF:

0.617

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

2-aminoadipic 2-oxoadipic aciduria

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Charcot-Marie-Tooth disease axonal type 2Q

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.039

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

(source)

DANN

Benign

0.41

DEOGEN2

Benign

0.048

T;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.22

T;T

MetaRNN

Benign

0.0000014

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-2.0

N;.

PhyloP100

6.8

PrimateAI

Uncertain

0.60

PROVEAN

Benign

2.4

N;N

REVEL

Benign

0.27

Sift

Benign

1.0

T;T

Sift4G

Benign

0.88

T;T

Polyphen

0.0

B;.

Vest4

0.067

MPC

0.20

ClinPred

0.013

GERP RS

4.2

PromoterAI

0.055

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.37

gMVP

0.54

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over