NM_152683.4(PRIMPOL):c.265T>G (p.Tyr89Asp) AND Myopia 22, autosomal dominant

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jan 6, 2020
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000055646.6

Allele description [Variation Report for NM_152683.4(PRIMPOL):c.265T>G (p.Tyr89Asp)]

NM_152683.4(PRIMPOL):c.265T>G (p.Tyr89Asp)

Gene:

PRIMPOL:primase and DNA directed polymerase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q35.1

Genomic location:

Preferred name:

NM_152683.4(PRIMPOL):c.265T>G (p.Tyr89Asp)

HGVS:

NC_000004.12:g.184659424T>G
NG_051582.1:g.14812T>G
NM_001300767.2:c.-123T>G
NM_001300768.2:c.265T>G
NM_001345891.2:c.265T>G
NM_001345892.2:c.265T>G
NM_001345893.2:c.265T>G
NM_001345894.2:c.-302T>G
NM_001345895.2:c.265T>G
NM_001345896.2:c.265T>G
NM_001345897.2:c.-302T>G
NM_001345898.2:c.-302T>G
NM_001345899.2:c.265T>G
NM_001345900.2:c.18T>G
NM_001345901.2:c.-302T>G
NM_152683.4:c.265T>GMANE SELECT
NP_001287697.1:p.Tyr89Asp
NP_001332820.1:p.Tyr89Asp
NP_001332821.1:p.Tyr89Asp
NP_001332822.1:p.Tyr89Asp
NP_001332824.1:p.Tyr89Asp
NP_001332825.1:p.Tyr89Asp
NP_001332828.1:p.Tyr89Asp
NP_001332829.1:p.Phe6Leu
NP_689896.1:p.Tyr89Asp
NC_000004.11:g.185580578T>G
NM_152683.2:c.265T>G
NM_152683.3:c.265T>G
NR_144312.2:n.570T>G
NR_144313.2:n.570T>G
NR_144314.2:n.573T>G

Protein change:

F6L; TYR89ASP

Links:

OMIM: 615421.0001; dbSNP: rs200857997

NCBI 1000 Genomes Browser:

rs200857997

Molecular consequence:

NM_001300767.2:c.-123T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001345894.2:c.-302T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001345897.2:c.-302T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001345898.2:c.-302T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001345901.2:c.-302T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001300768.2:c.265T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001345891.2:c.265T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001345892.2:c.265T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001345893.2:c.265T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001345895.2:c.265T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001345896.2:c.265T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001345899.2:c.265T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001345900.2:c.18T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_152683.4:c.265T>G - missense variant - [Sequence Ontology: SO:0001583]
NR_144312.2:n.570T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_144313.2:n.570T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_144314.2:n.573T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Myopia 22, autosomal dominant (MYP22)
Identifiers:: MONDO: MONDO:0014177; MedGen: C3809464; OMIM: 615420

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000083869	OMIM	no assertion criteria provided	Pathogenic (Aug 1, 2013)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001142340	Reproductive Health Research and Development, BGI Genomics	no assertion criteria provided	Uncertain significance (Jan 6, 2020)	germline	curation

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000083869

OMIM

no assertion criteria provided

Pathogenic
(Aug 1, 2013)

germline

literature only

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

SCV001142340

Reproductive Health Research and Development, BGI Genomics

no assertion criteria provided

Uncertain significance
(Jan 6, 2020)

germline

curation

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	curation
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Exome sequencing reveals CCDC111 mutation associated with high myopia.

Zhao F, Wu J, Xue A, Su Y, Wang X, Lu X, Zhou Z, Qu J, Zhou X.

Hum Genet. 2013 Aug;132(8):913-21. doi: 10.1007/s00439-013-1303-6. Epub 2013 Apr 12.

PubMed [citation]

PMID:: 23579484

Details of each submission

From OMIM, SCV000083869.2

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

Description

In affected members of a 4-generation Chinese family with autosomal dominant high myopia and 4 sporadic Chinese patients with myopia (MYP22; 615420), Zhao et al. (2013) identified heterozygosity for a c.265T-G transversion in exon 4 of the CCDC111 gene, resulting in a tyr89-to-asp (Y89D) substitution at a highly conserved residue. The mutation segregated with disease in the family and was not found in 270 Chinese controls. Because the severity of the clinical phenotype varied among the affected individuals, Zhao et al. (2013) suggested that environmental influences likely contributed to the etiology in the family and the sporadic patients.

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

From Reproductive Health Research and Development, BGI Genomics, SCV001142340.1

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

Description

NM_152683.3:c.265T>G in PRIMPOL gene has an allele frequency of 0.006 in East Asian subpopulation in the gnomAD database. The PRIMPOL gene is also known as CCDC111. Variants in the PRIMPOL gene is inherited as a dominant model. Since the phenotype (high myopia) is not lethal. The frequency in the genomAD cannot rule out its pathogenicity. Zhao et al reported a pedigree, both patient with high myopia and normal family memebers of which harbors this variant. It is suggested to be not full penetrance (PMID: 23579484). We interpret it as variant of uncertain significance (VUS).

#	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: Feb 4, 2024

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