NM_198880.3(QRICH1):c.1954C>T (p.Arg652Ter) AND Ververi-Brady syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 21, 2021
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:: RCV000627084.5

Allele description [Variation Report for NM_198880.3(QRICH1):c.1954C>T (p.Arg652Ter)]

NM_198880.3(QRICH1):c.1954C>T (p.Arg652Ter)

Gene:

QRICH1:glutamine rich 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p21.31

Genomic location:

Preferred name:

NM_198880.3(QRICH1):c.1954C>T (p.Arg652Ter)

HGVS:

NC_000003.12:g.49032715G>A
NG_012091.1:g.1728C>T
NM_001320580.2:c.1954C>T
NM_001320581.2:c.1954C>T
NM_001320582.2:c.1954C>T
NM_001320583.2:c.1954C>T
NM_001320584.1:c.1954C>T
NM_001320585.1:c.1954C>T
NM_017730.4:c.1954C>T
NM_198880.3:c.1954C>TMANE SELECT
NP_001307509.1:p.Arg652Ter
NP_001307510.1:p.Arg652Ter
NP_001307511.1:p.Arg652Ter
NP_001307512.1:p.Arg652Ter
NP_001307513.1:p.Arg652Ter
NP_001307514.1:p.Arg652Ter
NP_060200.2:p.Arg652Ter
NP_060200.2:p.Arg652Ter
NP_942581.1:p.Arg652Ter
NC_000003.11:g.49070148G>A
NM_017730.2:c.1954C>T
NM_017730.3:c.1954C>T

Protein change:

R652*; ARG652TER

Links:

OMIM: 617387.0001; dbSNP: rs1236702036

NCBI 1000 Genomes Browser:

rs1236702036

Molecular consequence:

NM_001320580.2:c.1954C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001320581.2:c.1954C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001320582.2:c.1954C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001320583.2:c.1954C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001320584.1:c.1954C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001320585.1:c.1954C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_017730.4:c.1954C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_198880.3:c.1954C>T - nonsense - [Sequence Ontology: SO:0001587]

Functional consequence:

loss_of_function_variant [Sequence Ontology: SO:0002054]

Condition(s)

Name:: Ververi-Brady syndrome
Identifiers:: MONDO: MONDO:0060707; MedGen: C4693824; OMIM: 617982

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000747894	OMIM	no assertion criteria provided	Pathogenic (Jun 4, 2021)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 28692176, 33009816
SCV002044402	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 21, 2021)	germline	research	PubMed (2) [See all records that cite these PMIDs] 34859529, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000747894

OMIM

no assertion criteria provided

Pathogenic
(Jun 4, 2021)

germline

literature only

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

SCV002044402

Institute of Human Genetics, University of Leipzig Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Dec 21, 2021)

germline

research

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	research
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Phenotypic spectrum associated with de novo mutations in QRICH1 gene.

Ververi A, Splitt M, Dean JCS; DDD Study., Brady AF.

Clin Genet. 2018 Feb;93(2):286-292. doi: 10.1111/cge.13096. Epub 2017 Dec 21.

PubMed [citation]

PMID:: 28692176

QRICH1 variants in Ververi-Brady syndrome-delineation of the genotypic and phenotypic spectrum.

Föhrenbach M, Jamra RA, Borkhardt A, Brozou T, Muschke P, Popp B, Rey LK, Schaper J, Surowy H, Zenker M, Zweier C, Wieczorek D, Redler S.

Clin Genet. 2021 Jan;99(1):199-207. doi: 10.1111/cge.13853. Epub 2020 Nov 10.

PubMed [citation]

PMID:: 33009816

See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000747894.2

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

Description

In an 8-year-old boy (patient 1) with Ververi-Brady syndrome (VERBRAS; 617982), Ververi et al. (2018) identified a de novo heterozygous c.1954C-T transition (c.1954C-T, NM_017730.2) in exon 9 of the QRICH1 gene, resulting in an arg652-to-ter (R652X) substitution in the DUF3504 domain. The mutation was found by trio-based exome sequencing and confirmed by Sanger sequencing. Functional studies of the variant and studies of patient cells were not performed, but the mutation was predicted to result in haploinsufficiency.

In a Vietnamese patient (patient 3) with VERBRAS, Fohrenbach et al. (2021) identified heterozygosity for the R652X mutation in the QRICH1 gene. The de novo mutation was identified by trio whole-exome sequencing. The mutation was not present in the gnomAD database. Functional studies were not performed.

#	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

From Institute of Human Genetics, University of Leipzig Medical Center, SCV002044402.1

#	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	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 30, 2023

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