NM_000020.3(ACVRL1):c.601C>T (p.Gln201Ter) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 1, 2022
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:: RCV000627226.2

Allele description [Variation Report for NM_000020.3(ACVRL1):c.601C>T (p.Gln201Ter)]

NM_000020.3(ACVRL1):c.601C>T (p.Gln201Ter)

Gene:

ACVRL1:activin A receptor like type 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q13.13

Genomic location:

Preferred name:

NM_000020.3(ACVRL1):c.601C>T (p.Gln201Ter)

Other names:

p.Gln201*

HGVS:

NC_000012.12:g.51914049C>T
NG_009549.1:g.11632C>T
NM_000020.3:c.601C>TMANE SELECT
NM_001077401.2:c.601C>T
NP_000011.2:p.Gln201Ter
NP_000011.2:p.Gln201Ter
NP_001070869.1:p.Gln201Ter
LRG_543t1:c.601C>T
LRG_543:g.11632C>T
LRG_543p1:p.Gln201Ter
NC_000012.11:g.52307833C>T
NM_000020.2:c.601C>T

Protein change:

Q201*

Links:

dbSNP: rs1318446539

NCBI 1000 Genomes Browser:

rs1318446539

Molecular consequence:

NM_000020.3:c.601C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001077401.2:c.601C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000748215	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Apr 16, 2018)	germline	clinical testing	Citation Link,
SCV004226859	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 1, 2022)	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

SCV000748215

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Apr 16, 2018)

germline

clinical testing

Citation Link,

SCV004226859

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 1, 2022)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	2	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 GeneDx, SCV000748215.3

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

Description

The Q201X variant in the ACVRL1 gene has been reported in an individual fulfilling three Curacao criteria for HHT due to a history of epistaxis, telangiectasias and a family history of HHT (Richards-Yutz et al., 2010). It has also been reported in another individual referred to an outside laboratory for HHT genetic testing, although no further clinical details were available (McDonald et al., 2011). Q201X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the ACVRL1 gene have been reported in the Human Gene Mutation Database in association with HHT (Stenson et al., 2014). Furthermore, the Q201X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016).

#	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 Mayo Clinic Laboratories, Mayo Clinic, SCV004226859.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (1)

Description

PM2_supporting, PS4_moderate, PVS1

#	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		2	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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