NM_001048174.2(MUTYH):c.1253_1255del (p.Phe418del) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 9, 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:: RCV000584316.8

Allele description [Variation Report for NM_001048174.2(MUTYH):c.1253_1255del (p.Phe418del)]

NM_001048174.2(MUTYH):c.1253_1255del (p.Phe418del)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

1p34.1

Genomic location:

Preferred name:

NM_001048174.2(MUTYH):c.1253_1255del (p.Phe418del)

HGVS:

NC_000001.11:g.45331321_45331323del
NG_008189.1:g.14150_14152del
NM_001048171.2:c.1253_1255del
NM_001048172.2:c.1256_1258del
NM_001048173.2:c.1253_1255del
NM_001048174.2:c.1253_1255delMANE SELECT
NM_001128425.2:c.1337_1339del
NM_001293190.2:c.1298_1300del
NM_001293191.2:c.1286_1288del
NM_001293192.2:c.977_979del
NM_001293195.2:c.1253_1255del
NM_001293196.2:c.977_979del
NM_001350650.2:c.908_910del
NM_001350651.2:c.908_910del
NM_012222.3:c.1328_1330del
NP_001041636.2:p.Phe418del
NP_001041637.1:p.Phe419del
NP_001041638.1:p.Phe418del
NP_001041639.1:p.Phe418del
NP_001121897.1:p.Phe446del
NP_001121897.1:p.Phe446del
NP_001280119.1:p.Phe433del
NP_001280120.1:p.Phe429del
NP_001280121.1:p.Phe326del
NP_001280124.1:p.Phe418del
NP_001280125.1:p.Phe326del
NP_001337579.1:p.Phe303del
NP_001337580.1:p.Phe303del
NP_036354.1:p.Phe443del
LRG_220t1:c.1337_1339del
LRG_220:g.14150_14152del
LRG_220p1:p.Phe446del
NC_000001.10:g.45796991_45796993del
NC_000001.10:g.45796993_45796995del
NM_001128425.1:c.1337_1339del
NM_001128425.1:c.1337_1339delTCT
NR_146882.2:n.1481_1483del
NR_146883.2:n.1330_1332del

Protein change:

F303del

Links:

dbSNP: rs747232389

NCBI 1000 Genomes Browser:

rs747232389

Molecular consequence:

NM_001048171.2:c.1253_1255del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001048172.2:c.1256_1258del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001048173.2:c.1253_1255del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001048174.2:c.1253_1255del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001128425.2:c.1337_1339del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001293190.2:c.1298_1300del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001293191.2:c.1286_1288del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001293192.2:c.977_979del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001293195.2:c.1253_1255del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001293196.2:c.977_979del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001350650.2:c.908_910del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001350651.2:c.908_910del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_012222.3:c.1328_1330del - inframe_deletion - [Sequence Ontology: SO:0001822]
NR_146882.2:n.1481_1483del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.1330_1332del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000690521	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 3, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001171085	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Feb 9, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000690521

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 3, 2020)

germline

clinical testing

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

SCV001171085

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Feb 9, 2024)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000690521.4

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

Description

This variant causes the deletion of a single amino acid, phenylalanine 446, in the MUTYH protein. This variant is also known as c.1295_1297del (p.Phe432del) based on an alternative transcript (NM_001048171). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 2/251496 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#	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 Ambry Genetics, SCV001171085.4

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

Description

The c.1337_1339delTCT variant (also known as p.F446del) is located in coding exon 14 of the MUTYH gene. This variant results from an in-frame TCT deletion at nucleotide positions 1337 to 1339. This results in the in-frame deletion of a phenylalanine at codon 446. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the available evidence, the clinical significance of this alteration remains unclear.

#	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

Last Updated: Sep 29, 2024

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