NM_001376.5(DYNC1H1):c.6994C>T (p.Arg2332Cys) AND Intellectual disability, autosomal dominant 13

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 12, 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:: RCV003223402.3

Allele description [Variation Report for NM_001376.5(DYNC1H1):c.6994C>T (p.Arg2332Cys)]

NM_001376.5(DYNC1H1):c.6994C>T (p.Arg2332Cys)

Gene:

DYNC1H1:dynein cytoplasmic 1 heavy chain 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q32.31

Genomic location:

Preferred name:

NM_001376.5(DYNC1H1):c.6994C>T (p.Arg2332Cys)

HGVS:

NC_000014.9:g.102012450C>T
NG_008777.1:g.52923C>T
NM_001376.5:c.6994C>TMANE SELECT
NP_001367.2:p.Arg2332Cys
NC_000014.8:g.102478787C>T
NM_001376.4:c.6994C>T

Protein change:

R2332C

Links:

dbSNP: rs1057518961

Molecular consequence:

NM_001376.5:c.6994C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Intellectual disability, autosomal dominant 13 (CDCBM13)
Synonyms:: CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 13
Identifiers:: MONDO: MONDO:0013805; MedGen: C3281202; OMIM: 614563

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003919013	Duke University Health System Sequencing Clinic, Duke University Health System	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 20, 2023)	de novo	research	PubMed (2) [See all records that cite these PMIDs] 25590979, 25741868
SCV005883666	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Dec 12, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25590979, 36175372 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003919013

Duke University Health System Sequencing Clinic, Duke University Health System

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 20, 2023)

de novo

research

PubMed (2)
[See all records that cite these PMIDs]

SCV005883666

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Dec 12, 2024)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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	de novo	yes	not provided	not provided	not provided	not provided	not provided	research

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

Whole-exome sequencing in undiagnosed genetic diseases: interpreting 119 trios.

Zhu X, Petrovski S, Xie P, Ruzzo EK, Lu YF, McSweeney KM, Ben-Zeev B, Nissenkorn A, Anikster Y, Oz-Levi D, Dhindsa RS, Hitomi Y, Schoch K, Spillmann RC, Heimer G, Marek-Yagel D, Tzadok M, Han Y, Worley G, Goldstein J, Jiang YH, Lancet D, et al.

Genet Med. 2015 Oct;17(10):774-81. doi: 10.1038/gim.2014.191. Epub 2015 Jan 15.

PubMed [citation]

PMID:: 25590979
PMCID:: PMC4791490

See all PubMed Citations (3)

Details of each submission

From Duke University Health System Sequencing Clinic, Duke University Health System, SCV003919013.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (2)

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005883666.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: DYNC1H1 c.6994C>T (p.Arg2332Cys) results in a non-conservative amino acid change located in the P-loop containing nucleoside triphosphate hydrolases (IPR027417) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. This variant was absent in gnomAD V4. c.6994C>T has been reported in the literature as a de novo occurrence in multiple individuals affected with Intellectual disability, autosomal dominant 13 (examples: Zhu_2015, Liu_2022, Internal data). These data indicate that the variant is likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 36175372, 25590979). ClinVar contains an entry for this variant (Variation ID: 374190). Based on the evidence outlined above, the variant was classified as pathogenic.

#	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: Apr 25, 2026

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