NM_198576.4(AGRN):c.1123G>T (p.Ala375Ser) AND Congenital myasthenic syndrome 8

Germline classification:: Benign (2 submissions)
Last evaluated:: Jan 29, 2024
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:: RCV000557729.11

Allele description [Variation Report for NM_198576.4(AGRN):c.1123G>T (p.Ala375Ser)]

NM_198576.4(AGRN):c.1123G>T (p.Ala375Ser)

Gene:

AGRN:agrin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.33

Genomic location:

Preferred name:

NM_198576.4(AGRN):c.1123G>T (p.Ala375Ser)

HGVS:

NC_000001.11:g.1041648G>T
NG_016346.1:g.26526G>T
NM_001305275.2:c.1123G>T
NM_001364727.2:c.808G>T
NM_198576.4:c.1123G>TMANE SELECT
NP_001292204.1:p.Ala375Ser
NP_001351656.1:p.Ala270Ser
NP_940978.2:p.Ala375Ser
LRG_198t1:c.1123G>T
LRG_198:g.26526G>T
NC_000001.10:g.977028G>T
NM_198576.2:c.1123G>T
NM_198576.3:c.1123G>T

Protein change:

A270S

Links:

dbSNP: rs138031468

NCBI 1000 Genomes Browser:

rs138031468

Molecular consequence:

NM_001305275.2:c.1123G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364727.2:c.808G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198576.4:c.1123G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Congenital myasthenic syndrome 8
Synonyms:: MYASTHENIC SYNDROME, CONGENITAL, DUE TO AGRIN DEFICIENCY; Myasthenic syndrome, congenital, 8, with pre- and postsynaptic defects
Identifiers:: MONDO: MONDO:0014052; MedGen: C3808739; Orphanet: 590; OMIM: 615120

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000653869	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Jan 29, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000883240	SIB Swiss Institute of Bioinformatics	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Oct 15, 2018)	germline	curation	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000653869

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Benign
(Jan 29, 2024)

germline

clinical testing

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

SCV000883240

SIB Swiss Institute of Bioinformatics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Benign
(Oct 15, 2018)

germline

curation

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, curation

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

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 Invitae, SCV000653869.8

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

#	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

From SIB Swiss Institute of Bioinformatics, SCV000883240.1

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

Description

This variant is interpreted as Benign, for Myasthenic syndrome, congenital, 8, autosomal recessive. The following ACMG Tag(s) were applied: BS1 => Allele frequency is greater than expected for disorder. BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age.

#	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 12, 2024

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