NM_015335.5(MED13L):c.3205C>T (p.Gln1069Ter) AND Cardiac anomalies - developmental delay - facial dysmorphism syndrome - ClinVar

NM_015335.5(MED13L):c.3205C>T (p.Gln1069Ter) AND Cardiac anomalies - developmental delay - facial dysmorphism syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 24, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002273192.3

Allele description [Variation Report for NM_015335.5(MED13L):c.3205C>T (p.Gln1069Ter)]

NM_015335.5(MED13L):c.3205C>T (p.Gln1069Ter)

Gene:

MED13L:mediator complex subunit 13L [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q24.21

Genomic location:

Preferred name:

NM_015335.5(MED13L):c.3205C>T (p.Gln1069Ter)

HGVS:

NC_000012.12:g.115991749G>A
NG_023366.1:g.290438C>T
NM_015335.5:c.3205C>TMANE SELECT
NP_056150.1:p.Gln1069Ter
NC_000012.11:g.116429554G>A
NM_015335.4:c.3205C>T

Protein change:

Q1069*

Links:

dbSNP: rs2137307819

NCBI 1000 Genomes Browser:

rs2137307819

Molecular consequence:

NM_015335.5:c.3205C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Cardiac anomalies - developmental delay - facial dysmorphism syndrome (MRFACD)
Identifiers:: MONDO: MONDO:0014773; MedGen: C4225208; Orphanet: 369891; OMIM: 616789

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002557897	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 24, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29511999, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002557897

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 24, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Smol T, Petit F, Piton A, Keren B, Sanlaville D, Afenjar A, Baker S, Bedoukian EC, Bhoj EJ, Bonneau D, Boudry-Labis E, Bouquillon S, Boute-Benejean O, Caumes R, Chatron N, Colson C, Coubes C, Coutton C, Devillard F, Dieux-Coeslier A, Doco-Fenzy M, Ewans LJ, et al.

Neurogenetics. 2018 May;19(2):93-103. doi: 10.1007/s10048-018-0541-0. Epub 2018 Mar 6.

PubMed [citation]

PMID:: 29511999

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

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002557897.2

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

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with impaired intellectual development and distinctive facial features with or without cardiac defects (MIM#616789). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0115 - Variants in this gene are known to have variable expressivity (PMID: 29511999). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. These variants have been reported many times as pathogenic (DECIPHER). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed, by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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

Last Updated: Jul 23, 2024

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