NM_012203.2(GRHPR):c.103del (p.Asp35fs) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 25, 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:: RCV000724161.13

Allele description [Variation Report for NM_012203.2(GRHPR):c.103del (p.Asp35fs)]

NM_012203.2(GRHPR):c.103del (p.Asp35fs)

Gene:

GRHPR:glyoxylate and hydroxypyruvate reductase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

9p13.2

Genomic location:

Preferred name:

NM_012203.2(GRHPR):c.103del (p.Asp35fs)

HGVS:

NC_000009.11:g.37424859del
NC_000009.12:g.37424864del
NG_008135.1:g.7155del
NM_012203.2:c.103delMANE SELECT
NP_036335.1:p.Asp35fs
NC_000009.11:g.37424859del
NC_000009.11:g.37424861del
NC_000009.11:g.37424861delG
NM_012203.1:c.103del
NM_012203.1:c.103delG
NM_012203.2:c.103delGMANE SELECT
p.Asp35ThrfsX11

Protein change:

D35fs

Links:

OMIM: 604296.0001; dbSNP: rs80356708

NCBI 1000 Genomes Browser:

rs80356708

Molecular consequence:

NM_012203.2:c.103del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000331674	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (May 2, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000941720	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 25, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 25644115, 10484776, 15327387, 28492532
SCV003919446	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Apr 20, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000331674

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Pathogenic
(May 2, 2016)

germline

clinical testing

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

Citation Link,

SCV000941720

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 25, 2024)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV003919446

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Apr 20, 2023)

germline

clinical testing

Citation Link

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
not provided	germline	unknown	2	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular analysis of the glyoxylate reductase (GRHPR) gene and description of mutations underlying primary hyperoxaluria type 2.

Cregeen DP, Williams EL, Hulton S, Rumsby G.

Hum Mutat. 2003 Dec;22(6):497.

PubMed [citation]

PMID:: 14635115

Phenotype-Genotype Correlations and Estimated Carrier Frequencies of Primary Hyperoxaluria.

Hopp K, Cogal AG, Bergstralh EJ, Seide BM, Olson JB, Meek AM, Lieske JC, Milliner DS, Harris PC; Rare Kidney Stone Consortium.

J Am Soc Nephrol. 2015 Oct;26(10):2559-70. doi: 10.1681/ASN.2014070698. Epub 2015 Feb 2.

PubMed [citation]

PMID:: 25644115
PMCID:: PMC4587693

See all PubMed Citations (5)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000331674.4

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

#	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		2	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000941720.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Asp35Thrfs*11) in the GRHPR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GRHPR are known to be pathogenic (PMID: 25644115). This variant is present in population databases (rs746720647, gnomAD 0.05%). This premature translational stop signal has been observed in individuals with primary hyperoxaluria (PMID: 10484776, 15327387). ClinVar contains an entry for this variant (Variation ID: 5636). For these reasons, this variant has been 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

From GeneDx, SCV003919446.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 16208537, 24116921, 18560364, 10484776, 31980526, 21228398, 14635115, 15327387, 11030416, 25644115, 28893421, 30609409, 31685312, 31589614)

#	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 29, 2024

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