NM_001330360.2(POLA1):c.2267A>G (p.Lys756Arg) AND X-linked intellectual disability, van Esch type

Germline classification:: Likely benign (1 submission)
Last evaluated:: Jul 17, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV004594290.2

Allele description [Variation Report for NM_001330360.2(POLA1):c.2267A>G (p.Lys756Arg)]

NM_001330360.2(POLA1):c.2267A>G (p.Lys756Arg)

Gene:

POLA1:DNA polymerase alpha 1, catalytic subunit [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp22.11

Genomic location:

Preferred name:

NM_001330360.2(POLA1):c.2267A>G (p.Lys756Arg)

HGVS:

NC_000023.11:g.24741425A>G
NG_016798.2:g.52479A>G
NM_001330360.2:c.2267A>GMANE SELECT
NM_001378303.1:c.2192A>G
NM_016937.4:c.2249A>G
NP_001317289.1:p.Lys756Arg
NP_001365232.1:p.Lys731Arg
NP_058633.2:p.Lys750Arg
NC_000023.10:g.24759542A>G
NM_001330360.1:c.2267A>G
NR_165482.1:n.1859A>G
NR_165483.1:n.2135A>G

Protein change:

K731R

Links:

dbSNP: rs2230928

NCBI 1000 Genomes Browser:

rs2230928

Molecular consequence:

NM_001330360.2:c.2267A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378303.1:c.2192A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_016937.4:c.2249A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_165482.1:n.1859A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165483.1:n.2135A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: X-linked intellectual disability, van Esch type
Synonyms:: MENTAL RETARDATION, X-LINKED, SYNDROMIC, VAN ESCH-O''DRISCOLL TYPE; Van Esch-O'Driscoll syndrome
Identifiers:: MONDO: MONDO:0015601; MedGen: C4305072; OMIM: 301030

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005086738	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jul 17, 2023)	germline	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

SCV005086738

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Jul 17, 2023)

germline

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

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 Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV005086738.2

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

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as likely benign. Following criteria are met: 0308 - Population frequency for this variant is out of keeping with known incidence of Van Esch-O'Driscoll syndrome (MIM#301030), with 124 hemizygotes and 2 homozygotes in gnomAD v3. (SB) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting 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

Last Updated: May 16, 2025

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