NM_001048174.2(MUTYH):c.1253_1255del (p.Phe418del) AND Familial adenomatous polyposis 2

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 26, 2023
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:: RCV000640372.9

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:: Familial adenomatous polyposis 2
Synonyms:: COLORECTAL ADENOMATOUS POLYPOSIS, AUTOSOMAL RECESSIVE; ADENOMAS, MULTIPLE COLORECTAL, AUTOSOMAL RECESSIVE; MYH-associated polyposis; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012041; MedGen: C3272841; Orphanet: 220460; OMIM: 608456

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Klebsiella sp. Z1 16S ribosomal RNA gene, partial sequence
Klebsiella sp. Z1 16S ribosomal RNA gene, partial sequence
gi|606241215|gb|KJ149816.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000761961	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 13, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004198800	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 26, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000761961

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 13, 2023)

germline

clinical testing

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

SCV004198800

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 26, 2023)

unknown

clinical testing

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

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000761961.6

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

Description

This variant, c.1337_1339del, results in the deletion of 1 amino acid(s) of the MUTYH protein (p.Phe446del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs747232389, gnomAD 0.003%). This variant has been observed in individual(s) with clinical features of MUTYH-associated polyposis (Invitae). ClinVar contains an entry for this variant (Variation ID: 492014). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been 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 Baylor Genetics, SCV004198800.1

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

Last Updated: Sep 29, 2024

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