NM_000548.5(TSC2):c.4638C>T (p.Ala1546=) AND not specified

Germline classification:: Benign (4 submissions)
Last evaluated:: Oct 30, 2017
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:: RCV000125691.22

Allele description [Variation Report for NM_000548.5(TSC2):c.4638C>T (p.Ala1546=)]

NM_000548.5(TSC2):c.4638C>T (p.Ala1546=)

Gene:

TSC2:TSC complex subunit 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_000548.5(TSC2):c.4638C>T (p.Ala1546=)

Other names:

p.A1546A:GCC>GCT; p.Ala1546Ala

HGVS:

NC_000016.10:g.2085298C>T
NG_005895.1:g.40993C>T
NM_000548.5:c.4638C>TMANE SELECT
NM_001077183.3:c.4437C>T
NM_001114382.3:c.4569C>T
NM_001318827.2:c.4329C>T
NM_001318829.2:c.4293C>T
NM_001318831.2:c.3906C>T
NM_001318832.2:c.4470C>T
NM_001363528.2:c.4440C>T
NM_001370404.1:c.4506C>T
NM_001370405.1:c.4509C>T
NM_021055.3:c.4509C>T
NP_000539.2:p.Ala1546=
NP_001070651.1:p.Ala1479=
NP_001107854.1:p.Ala1523=
NP_001305756.1:p.Ala1443=
NP_001305758.1:p.Ala1431=
NP_001305760.1:p.Ala1302=
NP_001305761.1:p.Ala1490=
NP_001350457.1:p.Ala1480=
NP_001357333.1:p.Ala1502=
NP_001357334.1:p.Ala1503=
NP_066399.2:p.Ala1503=
LRG_487t1:c.4638C>T
LRG_487:g.40993C>T
NC_000016.9:g.2135299C>T
NM_000548.3:c.4638C>T
NM_000548.4:c.4638C>T
p.A1546A
p.(=)

Links:

Tuberous sclerosis database (TSC2): TSC2_00958; dbSNP: rs45517354

NCBI 1000 Genomes Browser:

rs45517354

Molecular consequence:

NM_000548.5:c.4638C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001077183.3:c.4437C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001114382.3:c.4569C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001318827.2:c.4329C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001318829.2:c.4293C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001318831.2:c.3906C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001318832.2:c.4470C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001363528.2:c.4440C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001370404.1:c.4506C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001370405.1:c.4509C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_021055.3:c.4509C>T - synonymous variant - [Sequence Ontology: SO:0001819]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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PREDICTED: Homo sapiens CYFIP related Rac1 interactor A (CYRIA), transcript vari...
PREDICTED: Homo sapiens CYFIP related Rac1 interactor A (CYRIA), transcript variant X7, mRNA
gi|2217331270|ref|XM_047445941.1|

Nucleotide
IDH1 [Glycine max]
IDH1 [Glycine max]
Gene ID:606295

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000169155	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Benign (Oct 31, 2013)	germline	clinical testing	Citation Link,
SCV000305228	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000967123	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Benign (Feb 21, 2013)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002066262	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Oct 30, 2017)	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	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	1	1	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

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, SCV000169155.12

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

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

#	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 PreventionGenetics, part of Exact Sciences, SCV000305228.1

#	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 Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000967123.1

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

Description

Ala1546Ala in exon 36 of TSC2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 1.3% (59/4392) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs45517354).

#	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		1	not provided	1	not provided

From Genetic Services Laboratory, University of Chicago, SCV002066262.1

#	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	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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