NM_004643.4(PABPN1):c.3GGC[9] (p.Ala11_Gly12insAlaAla) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 1, 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:: RCV000288768.27

Allele description [Variation Report for NM_004643.4(PABPN1):c.3GGC[9] (p.Ala11_Gly12insAlaAla)]

NM_004643.4(PABPN1):c.3GGC[9] (p.Ala11_Gly12insAlaAla)

Genes:

BCL2L2-PABPN1:BCL2L2-PABPN1 readthrough [Gene - HGNC]
PABPN1:poly(A) binding protein nuclear 1 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

14q11.2

Genomic location:

Preferred name:

NM_004643.4(PABPN1):c.3GGC[9] (p.Ala11_Gly12insAlaAla)

HGVS:

NC_000014.9:g.23321472GGC[9]
NG_008239.1:g.6285GGC[9]
NG_128768.1:g.363GGC[9]
NM_001199864.3:c.433-709GGC[9]
NM_001360551.3:c.3GGC[9]
NM_001387340.1:c.550-709GGC[9]
NM_001387341.1:c.529-709GGC[9]
NM_001387342.1:c.529-709GGC[9]
NM_001387343.1:c.529-709GGC[9]
NM_001387344.1:c.529-709GGC[9]
NM_001387345.1:c.433-709GGC[9]
NM_001387346.1:c.433-709GGC[9]
NM_004643.4:c.3GGC[9]MANE SELECT
NP_001347480.1:p.Ala11_Gly12insAlaAla
NP_004634.1:p.Ala11_Gly12insAlaAla
NC_000014.8:g.23790681GGC[9]
NM_004643.3:c.18_23dupGGCGGC

Links:

dbSNP: rs193922941

NCBI 1000 Genomes Browser:

rs193922941

Molecular consequence:

NM_001360551.3:c.3GGC[9] - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_004643.4:c.3GGC[9] - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001360551.3:c.3GGC[9] - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_004643.4:c.3GGC[9] - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001199864.3:c.433-709GGC[9] - intron variant - [Sequence Ontology: SO:0001627]
NM_001387340.1:c.550-709GGC[9] - intron variant - [Sequence Ontology: SO:0001627]
NM_001387341.1:c.529-709GGC[9] - intron variant - [Sequence Ontology: SO:0001627]
NM_001387342.1:c.529-709GGC[9] - intron variant - [Sequence Ontology: SO:0001627]
NM_001387343.1:c.529-709GGC[9] - intron variant - [Sequence Ontology: SO:0001627]
NM_001387344.1:c.529-709GGC[9] - intron variant - [Sequence Ontology: SO:0001627]
NM_001387345.1:c.433-709GGC[9] - intron variant - [Sequence Ontology: SO:0001627]
NM_001387346.1:c.433-709GGC[9] - intron variant - [Sequence Ontology: SO:0001627]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000330133	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (May 24, 2018)	germline	clinical testing	Citation Link,
SCV001248587	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Apr 1, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000330133

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(May 24, 2018)

germline

clinical testing

Citation Link,

SCV001248587

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Apr 1, 2023)

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	yes	4	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000330133.5

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

Description

The c.18_23dupGGCGGC pathogenic variant in the PABPN1 gene has been reported previously in individuals with oculopharyngeal muscular dystrophy in four families (Brais et al., 1998). This duplication is in the region of the polyalanine tract in exon 1, and other duplications nearby have been reported in the Human Gene Mutation Database in association with oculopharyngeal muscular dystrophy (Stenson et al., 2014). The c.18_23dupGGCGGC variant causes an in-frame duplication of 2 alanine residues, denoted p.Ala10_Ala11dup. The result of this variant is a polyalanine tract length of 12 in this individual. The c.18_23dupGGCGGC variant was not observed in approximately 192 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.18_23dupGGCGGC as a pathogenic variant.

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

From CeGaT Center for Human Genetics Tuebingen, SCV001248587.25

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	not provided	clinical testing	not provided

Description

PABPN1: PM1:Strong, PM2, PP1:Moderate, PP4:Moderate, PS4:Moderate

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		4	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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