NM_018706.7:c.814T>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -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. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 1168372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-12089082-T-G is described in Lovd as [Benign].

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

GnomAD3 exomes

AF:

0.556

AC:

139871

AN:

251450

Hom.:

40779

AF XY:

0.574

AC XY:

78032

AN XY:

135896

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 SAS exome

AF:

0.723

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

Gnomad4 AFR exome

AF:

0.246

Gnomad4 AMR exome

AF:

0.495

Gnomad4 ASJ exome

AF:

0.657

Gnomad4 EAS exome

AF:

0.492

Gnomad4 SAS exome

AF:

0.719

Gnomad4 FIN exome

AF:

0.483

Gnomad4 NFE exome

AF:

0.594

Gnomad4 OTH exome

AF:

0.567

GnomAD4 genome

AF:

0.486

AC:

73834

AN:

151956

Hom.:

19735

Cov.:

AF XY:

0.487

AC XY:

36183

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.258

Gnomad4 AMR

AF:

0.538

Gnomad4 ASJ

AF:

0.650

Gnomad4 EAS

AF:

0.467

Gnomad4 SAS

AF:

0.720

Gnomad4 FIN

AF:

0.471

Gnomad4 NFE

AF:

0.588

Gnomad4 OTH

AF:

0.524

Alfa

AF:

0.581

Hom.:

63252

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

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

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

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

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

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;.

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

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.37

gMVP

0.54

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over