Genetic Variant MUTYH:c. (chr1-45331832-A-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is The variant received 2 classification points (ACGS-UK Somatic Oncogenicity v2025): 2P and 0B. O3_Moderate

The NM_001128425.2(MUTYH):c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The gene MUTYH is a cancer driver gene (CancerMine: 2 driver citations). The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

MUTYH
NM_001128425.2 exon_region

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.265

Publications

0 publications found

Variant links:

Genes affected

MUTYH (HGNC:7527): (mutY DNA glycosylase) This gene encodes a DNA glycosylase involved in oxidative DNA damage repair. The enzyme excises adenine bases from the DNA backbone at sites where adenine is inappropriately paired with guanine, cytosine, or 8-oxo-7,8-dihydroguanine, a major oxidatively damaged DNA lesion. The protein is localized to the nucleus and mitochondria. This gene product is thought to play a role in signaling apoptosis by the introduction of single-strand breaks following oxidative damage. Mutations in this gene result in heritable predisposition to colorectal cancer, termed MUTYH-associated polyposis (MAP). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2017]

MUTYH Gene-Disease associations (from GenCC):

familial adenomatous polyposis 2
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, G2P, ClinGen
colorectal cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
familial ovarian cancer
Inheritance: AD, AR Classification: NO_KNOWN Submitted by: ClinGen
hereditary breast carcinoma
Inheritance: AD, AR Classification: NO_KNOWN Submitted by: ClinGen

MUTYH links:

ENSG00000288208 (HGNC:):

ENSG00000288208 links:

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new If you want to explore the variant's impact on the transcript NM_001128425.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 points.

Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = absent, AC = 0 — absent/extremely rare (O3 moderate [+2])

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001128425.2. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MUTYH	NM_001128425.2	MANE Plus Clinical	c.	exon_region	Exon 12 of 16	NP_001121897.1	E5KP25
MUTYH	NM_001048174.2	MANE Select	c.	exon_region	Exon 12 of 16	NP_001041639.1	Q9UIF7-6
MUTYH	NM_012222.3		c.	exon_region	Exon 12 of 16	NP_036354.1	Q9UIF7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MUTYH	ENST00000710952.2	MANE Plus Clinical	c.	exon_region	Exon 12 of 16	ENSP00000518552.2	E5KP25
MUTYH	ENST00000456914.7	TSL:1 MANE Select	c.	exon_region	Exon 12 of 16	ENSP00000407590.2	Q9UIF7-6
MUTYH	ENST00000372098.7	TSL:1	c.	exon_region	Exon 12 of 16	ENSP00000361170.3	Q9UIF7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.27

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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MUTYH p.Gln338Gln

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACGS-UK Somatic Oncogenicity v2025

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over