NM_018706.7(DHTKD1):c.104C>T (p.Pro35Leu) AND 2-aminoadipic 2-oxoadipic aciduria

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 3, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000714644.9

Allele description [Variation Report for NM_018706.7(DHTKD1):c.104C>T (p.Pro35Leu)]

NM_018706.7(DHTKD1):c.104C>T (p.Pro35Leu)

Genes:

LOC130003343:ATAC-STARR-seq lymphoblastoid silent region 2137 [Gene]
DHTKD1:dehydrogenase E1 and transketolase domain containing 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10p14

Genomic location:

Preferred name:

NM_018706.7(DHTKD1):c.104C>T (p.Pro35Leu)

HGVS:

NC_000010.11:g.12069137C>T
NG_033248.1:g.5221C>T
NM_018706.5:c.104C>T
NM_018706.7:c.104C>TMANE SELECT
NP_061176.4:p.Pro35Leu
NC_000010.10:g.12111136C>T
NM_018706.6:c.104C>T

Protein change:

P35L

Links:

dbSNP: rs753355529

NCBI 1000 Genomes Browser:

rs753355529

Molecular consequence:

NM_018706.7:c.104C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: 2-aminoadipic 2-oxoadipic aciduria (AAKAD)
Synonyms:: Aminoadipic aciduria; ALPHA-AMINOADIPIC AND ALPHA-KETOADIPIC ACIDURIA
Identifiers:: MONDO: MONDO:0008774; MedGen: C1859817; Orphanet: 79154; OMIM: 204750

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000845360	Genomic Research Center, Shahid Beheshti University of Medical Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 7, 2018)	inherited	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002307855	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 3, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000845360

Genomic Research Center, Shahid Beheshti University of Medical Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Aug 7, 2018)

inherited

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002307855

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 3, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	inherited	no	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Genomic Research Center, Shahid Beheshti University of Medical Sciences, SCV000845360.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	no	not provided	not provided	not provided		1	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002307855.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 35 of the DHTKD1 protein (p.Pro35Leu). This variant is present in population databases (rs753355529, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with DHTKD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 587471). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 22, 2024

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