NM_001048174.2(MUTYH):c.32G>A (p.Gly11Asp) AND not provided

Germline classification:: Benign/Likely benign (6 submissions)
Last evaluated:: Aug 1, 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:: RCV000034680.37

Allele description [Variation Report for NM_001048174.2(MUTYH):c.32G>A (p.Gly11Asp)]

NM_001048174.2(MUTYH):c.32G>A (p.Gly11Asp)

Gene:

MUTYH:mutY DNA glycosylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p34.1

Genomic location:

Preferred name:

NM_001048174.2(MUTYH):c.32G>A (p.Gly11Asp)

Other names:

p.G25D:GGT>GAT

HGVS:

NC_000001.11:g.45334474C>T
NG_008189.1:g.10997G>A
NM_001048171.2:c.32G>A
NM_001048172.2:c.32G>A
NM_001048173.2:c.32G>A
NM_001048174.2:c.32G>AMANE SELECT
NM_001128425.2:c.74G>A
NM_001293190.2:c.74G>A
NM_001293191.2:c.32G>A
NM_001293192.2:c.-181G>A
NM_001293195.2:c.32G>A
NM_001293196.2:c.-181G>A
NM_001350650.2:c.-240G>A
NM_001350651.2:c.-176G>A
NM_012222.3:c.74G>A
NP_001041636.1:p.Gly25Asp
NP_001041636.2:p.Gly11Asp
NP_001041637.1:p.Gly11Asp
NP_001041638.1:p.Gly11Asp
NP_001041639.1:p.Gly11Asp
NP_001121897.1:p.Gly25Asp
NP_001121897.1:p.Gly25Asp
NP_001280119.1:p.Gly25Asp
NP_001280120.1:p.Gly11Asp
NP_001280124.1:p.Gly11Asp
NP_036354.1:p.Gly25Asp
NP_036354.1:p.Gly25Asp
LRG_220t1:c.74G>A
LRG_220:g.10997G>A
LRG_220p1:p.Gly25Asp
NC_000001.10:g.45800146C>T
NM_001048171.1:c.74G>A
NM_001128425.1:c.74G>A
NM_012222.2:c.74G>A
NR_146882.2:n.260G>A
NR_146883.2:n.183G>A
p.G25D

Protein change:

G11D

Links:

dbSNP: rs75321043

NCBI 1000 Genomes Browser:

rs75321043

Molecular consequence:

NM_001293192.2:c.-181G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001293196.2:c.-181G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001350650.2:c.-240G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001350651.2:c.-176G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001048171.2:c.32G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001048172.2:c.32G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001048173.2:c.32G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001048174.2:c.32G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001128425.2:c.74G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293190.2:c.74G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293191.2:c.32G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293195.2:c.32G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_012222.3:c.74G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_146882.2:n.260G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.183G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV000043379	Biesecker Lab/Clinical Genomics Section, National Institutes of Health - ClinSeq	no assertion criteria provided	variant of unknown significance (Jul 13, 2012)	germline	research	PubMed (1) [See all records that cite this PMID]
SCV000211396	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely benign (Jun 11, 2021)	germline	clinical testing	Citation Link,
SCV000697710	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Aug 21, 2017)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 25820570, 26684191, 18811933, 26332594, 22703879, 24728327, 27443514 LabCorp Variant Classification Summary - May 2015.docx, Citation Link,
SCV001147275	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Benign (Aug 1, 2024)	germline	clinical testing	Citation Link,
SCV001159515	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Benign (Apr 28, 2023)	germline	clinical testing	Citation Link,
SCV001469577	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Likely benign (Jun 29, 2023)	unknown	clinical testing	PubMed (22) [See all records that cite these PMIDs] 29879026, 30333958, 29667044, 33194656, 33094510, 33309985, 18422726, 24728327, 22703879, 25820570, 22641385, 26332594, 16929514, 18811933, 17252231, 11295288, 26684191, 25980754, 17703316, 27443514, 26900293, 26467025

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	1	not provided	not provided	572	not provided	research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	3	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Germline mutation of CHEK2 in neurofibromatosis 1 and 2: Two case reports.

Li Q, Zhao F, Ju Y.

Medicine (Baltimore). 2018 Jun;97(23):e10894. doi: 10.1097/MD.0000000000010894.

PubMed [citation]

PMID:: 29879026
PMCID:: PMC5999503

The Ethnic-Specific Spectrum of Germline Nucleotide Variants in DNA Damage Response and Repair Genes in Hereditary Breast and Ovarian Cancer Patients of Tatar Descent.

Brovkina OI, Shigapova L, Chudakova DA, Gordiev MG, Enikeev RF, Druzhkov MO, Khodyrev DS, Shagimardanova EI, Nikitin AG, Gusev OA.

Front Oncol. 2018;8:421. doi: 10.3389/fonc.2018.00421.

PubMed [citation]

PMID:: 30333958
PMCID:: PMC6176317

See all PubMed Citations (22)

Details of each submission

From Biesecker Lab/Clinical Genomics Section, National Institutes of Health - ClinSeq, SCV000043379.1

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

Description

The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See PubMed ID:22703879 for details.

Description

Converted during submission to Uncertain significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	572	not provided	discovery		1	not provided	not provided	not provided

From GeneDx, SCV000211396.12

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

Description

This variant is associated with the following publications: (PMID: 18422726, 22641385, 22703879, 11295288, 17252231, 30333958, 29879026, 18811933, 16929514, 25820570, 26684191, 26900293, 25980754, 27443514, 26332594, 24728327, 17703316, 27600092, 29330641, 29667044)

#	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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697710.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

Variant summary: The MUTYH c.74G>A (p.Gly25Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in the large and broad cohorts of the ExAC project at an allele frequency of 0.001112 (135/121410 chrs tested), predominantly observed in the East Asian subpopulation (0.013; 114/8654 chrs, including 2 homozygotes). This frequency is about 3 times the estimated maximal expected allele frequency of a pathogenic MUTYH variant (0.0045644), suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. Most of the published reports indicate that c.74G>A co-occurs in cis with c.53C>T (P18L). Although c.[53C>T; 74G>A] haplotype has been reported to be enriched in sporadic CRC pts compared to controls (Chen, 2008), in functional studies both the complex allele and its compounds were shown to retain complementation ability and were considered to be functionally neutral. In addition, several reported CRC pts carried known pathogenic variants (APC c.3595_3596delAA (p.Lys1199Glufs), MSH6 c.3724_3726del (p.Arg1242del) , that could have explain CRC phenotype in these families (Taki, 2016, Ring, 2012). Lastly, several reputable databases/diagnostic centers classified the variant of interest as VUS/ Benign. Taking together, by applying ACMG rules, the variant was classified as Benign.

#	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 CeGaT Center for Human Genetics Tuebingen, SCV001147275.16

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	not provided

Description

MUTYH: BS1, BS2

#	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		3	not provided	not provided	not provided

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001159515.5

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

#	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 Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001469577.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (22)

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

Last Updated: Oct 20, 2024

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