NM_005120.3(MED12):c.5111G>A (p.Trp1704Ter) AND Cholestasis-pigmentary retinopathy-cleft palate syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 16, 2021
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV001796997.1

Allele description [Variation Report for NM_005120.3(MED12):c.5111G>A (p.Trp1704Ter)]

NM_005120.3(MED12):c.5111G>A (p.Trp1704Ter)

Gene:

MED12:mediator complex subunit 12 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq13.1

Genomic location:

Preferred name:

NM_005120.3(MED12):c.5111G>A (p.Trp1704Ter)

HGVS:

NC_000023.11:g.71136366G>A
NG_012808.1:g.22811G>A
NM_005120.3:c.5111G>AMANE SELECT
NP_005111.2:p.Trp1704Ter
NC_000023.10:g.70356216G>A

Protein change:

W1704*; TRP1704TER

Links:

OMIM: 300188.0008; dbSNP: rs2147826070

NCBI 1000 Genomes Browser:

rs2147826070

Molecular consequence:

NM_005120.3:c.5111G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Cholestasis-pigmentary retinopathy-cleft palate syndrome (HDKR)
Synonyms:: Hardikar syndrome
Identifiers:: MONDO: MONDO:0012997; MeSH: C535632; MedGen: C0795969; Orphanet: 1415; OMIM: 301068

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MULTISPECIES: 30S ribosomal protein S21 [Bacteria]
MULTISPECIES: 30S ribosomal protein S21 [Bacteria]
gi|489244775|ref|WP_003152957.1|

Protein
MAPK cascade adaptor protein Ste4 [Schizosaccharomyces pombe]
MAPK cascade adaptor protein Ste4 [Schizosaccharomyces pombe]
gi|19114195|ref|NP_593283.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002037207	OMIM	no assertion criteria provided	Pathogenic (Dec 16, 2021)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 33244166, 9286458

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002037207

OMIM

no assertion criteria provided

Pathogenic
(Dec 16, 2021)

germline

literature only

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

De novo loss-of-function variants in X-linked MED12 are associated with Hardikar syndrome in females.

Li D, Strong A, Shen KM, Cassiman D, Van Dyck M, Linhares ND, Valadares ER, Wang T, Pena SDJ, Jaeken J, Vergano S, Zackai E, Hing A, Chow P, Ganguly A, Scholz T, Bierhals T, Philipp D, Hakonarson H, Bhoj E.

Genet Med. 2021 Apr;23(4):637-644. doi: 10.1038/s41436-020-01031-7. Epub 2020 Nov 27.

PubMed [citation]

PMID:: 33244166

Hardikar syndrome: a new syndrome with cleft lip/palate, pigmentary retinopathy and cholestasis.

Cools F, Jaeken J.

Am J Med Genet. 1997 Sep 5;71(4):472-4.

PubMed [citation]

PMID:: 9286458

Details of each submission

From OMIM, SCV002037207.1

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

Description

In a 21-year-old woman (patient 5) with Hardikar syndrome (HDKR; 301068), Li et al. (2021) identified a presumed de novo heterozygous c.5111G-A transition in the MED12 gene, predicted to result in a trp1704-to-ter (W1704X) substitution. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was predicted to lead to nonsense-mediated mRNA decay, resulting in haploinsufficiency. Functional studies of the variant were not performed. Patient cells showed skewed X inactivation (99:1). The patient died at age 21 years from an intracranial hemorrhage. The patient had previously been reported by Cools and Jaeken (1997).

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

Last Updated: Dec 24, 2023

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