NM_001031710.3(KLHL7):c.1051C>T (p.Arg351Ter) AND PERCHING syndrome

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Sep 1, 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:: RCV000991230.3

Allele description [Variation Report for NM_001031710.3(KLHL7):c.1051C>T (p.Arg351Ter)]

NM_001031710.3(KLHL7):c.1051C>T (p.Arg351Ter)

Gene:

KLHL7:kelch like family member 7 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p15.3

Genomic location:

Preferred name:

NM_001031710.3(KLHL7):c.1051C>T (p.Arg351Ter)

HGVS:

NC_000007.14:g.23165812C>T
NG_016983.2:g.65079C>T
NM_001031710.3:c.1051C>TMANE SELECT
NM_018846.5:c.907C>T
NP_001026880.2:p.Arg351Ter
NP_061334.4:p.Arg303Ter
NC_000007.13:g.23205431C>T
NG_016983.1:g.65079C>T
NM_001031710.2:c.1051C>T
NR_033328.2:n.1424C>T

Protein change:

R303*; ARG351TER

Links:

OMIM: 611119.0009; dbSNP: rs746612410

NCBI 1000 Genomes Browser:

rs746612410

Molecular consequence:

NR_033328.2:n.1424C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001031710.3:c.1051C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_018846.5:c.907C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: PERCHING syndrome (PERCHING)
Synonyms:: Cold-induced sweating syndrome 3
Identifiers:: MONDO: MONDO:0014890; MedGen: C4310742; Orphanet: 157820; OMIM: 617055

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001142626	OMIM	no assertion criteria provided	Pathogenic (Jan 9, 2020)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001167486	Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	no assertion criteria provided	Pathogenic	inherited	research
SCV002573364	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 1, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30426380, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001142626

OMIM

no assertion criteria provided

Pathogenic
(Jan 9, 2020)

germline

literature only

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

SCV001167486

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

no assertion criteria provided

Pathogenic

inherited

research

SCV002573364

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 1, 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	inherited	yes	4	1	not provided	not provided	yes	research
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Expanding the clinical spectrum of recessive truncating mutations of KLHL7 to a Bohring-Opitz-like phenotype.

Bruel AL, Bigoni S, Kennedy J, Whiteford M, Buxton C, Parmeggiani G, Wherlock M, Woodward G, Greenslade M, Williams M, St-Onge J, Ferlini A, Garani G, Ballardini E, van Bon BW, Acuna-Hidalgo R, Bohring A, Deleuze JF, Boland A, Meyer V, Olaso R, Ginglinger E, et al.

J Med Genet. 2017 Dec;54(12):830-835. doi: 10.1136/jmedgenet-2017-104748. Epub 2017 Oct 26.

PubMed [citation]

PMID:: 29074562

Comparison of clinical parameters with whole exome sequencing analysis results of autosomal recessive patients; a center experience.

Elmas M, Yıldız H, Erdoğan M, Gogus B, Avcı K, Solak M.

Mol Biol Rep. 2019 Feb;46(1):287-299. doi: 10.1007/s11033-018-4470-7. Epub 2018 Nov 13.

PubMed [citation]

PMID:: 30426380

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV001142626.1

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

Description

In 2 sibs, aged 19 and 22 years and born of unrelated parents, with PERCHING syndrome (617055), Bruel et al. (2017) identified a homozygous mutation (NM_018846.4) in the KLHL7 gene, resulting in an arg351-to-ter (R351X) substitution in the Kelch-repeat domain. The variant, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in public genomic databases, including ExAC. Functional studies of the variant and studies of patient cells 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 Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine, SCV001167486.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	yes	research	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	yes	not provided	not provided	not provided		4	not provided	1	not provided

From 3billion, SCV002573364.1

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

Description

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). Stop-gained (nonsense) is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic without evidence for the classification (ClinVar ID: VCV000804273 / PMID: 30426380). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Oct 8, 2024

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