NM_000548.5(TSC2):c.2537del (p.Phe846fs) AND Tuberous sclerosis 2

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 1, 2022
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:: RCV002283947.1

Allele description [Variation Report for NM_000548.5(TSC2):c.2537del (p.Phe846fs)]

NM_000548.5(TSC2):c.2537del (p.Phe846fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_000548.5(TSC2):c.2537del (p.Phe846fs)

HGVS:

NC_000016.10:g.2074381del
NG_005895.1:g.30076del
NM_000548.5:c.2537delMANE SELECT
NM_001077183.3:c.2537del
NM_001114382.3:c.2537del
NM_001318827.2:c.2426del
NM_001318829.2:c.2390del
NM_001318831.2:c.1937del
NM_001318832.2:c.2570del
NM_001363528.2:c.2537del
NM_001370404.1:c.2537del
NM_001370405.1:c.2537del
NM_001406663.1:c.2537delT
NM_001406664.1:c.2537delT
NM_001406665.1:c.2537delT
NM_001406667.1:c.2627delT
NM_001406668.1:c.2627delT
NM_001406670.1:c.2426delT
NM_001406671.1:c.2525delT
NM_001406673.1:c.2525delT
NM_001406675.1:c.2390delT
NM_001406676.1:c.2390delT
NM_001406677.1:c.2480delT
NM_001406678.1:c.2426delT
NM_001406679.1:c.2390delT
NM_001406680.1:c.1937delT
NM_001406681.1:c.2075delT
NM_001406682.1:c.1937delT
NM_001406683.1:c.1937delT
NM_001406684.1:c.1937delT
NM_001406685.1:c.1937delT
NM_001406686.1:c.1937delT
NM_001406687.1:c.1937delT
NM_001406688.1:c.1937delT
NM_001406689.1:c.1193delT
NM_001406690.1:c.1193delT
NM_001406691.1:c.1193delT
NM_001406692.1:c.1193delT
NM_001406693.1:c.1193delT
NM_001406694.1:c.1193delT
NM_001406695.1:c.1193delT
NM_001406696.1:c.1193delT
NM_001406697.1:c.1193delT
NM_001406698.1:c.935delT
NM_021055.3:c.2537del
NP_000539.2:p.Phe846Serfs
NP_000539.2:p.Phe846fs
NP_001070651.1:p.Phe846fs
NP_001107854.1:p.Phe846fs
NP_001305756.1:p.Phe809fs
NP_001305758.1:p.Phe797fs
NP_001305760.1:p.Phe646fs
NP_001305761.1:p.Phe857fs
NP_001350457.1:p.Phe846fs
NP_001357333.1:p.Phe846fs
NP_001357334.1:p.Phe846fs
NP_001393592.1:p.Phe846Serfs
NP_001393593.1:p.Phe846Serfs
NP_001393594.1:p.Phe846Serfs
NP_001393596.1:p.Phe876Serfs
NP_001393597.1:p.Phe876Serfs
NP_001393599.1:p.Phe809Serfs
NP_001393600.1:p.Phe842Serfs
NP_001393602.1:p.Phe842Serfs
NP_001393604.1:p.Phe797Serfs
NP_001393605.1:p.Phe797Serfs
NP_001393606.1:p.Phe827Serfs
NP_001393607.1:p.Phe809Serfs
NP_001393608.1:p.Phe797Serfs
NP_001393609.1:p.Phe646Serfs
NP_001393610.1:p.Phe692Serfs
NP_001393611.1:p.Phe646Serfs
NP_001393612.1:p.Phe646Serfs
NP_001393613.1:p.Phe646Serfs
NP_001393614.1:p.Phe646Serfs
NP_001393615.1:p.Phe646Serfs
NP_001393616.1:p.Phe646Serfs
NP_001393617.1:p.Phe646Serfs
NP_001393618.1:p.Phe398Serfs
NP_001393619.1:p.Phe398Serfs
NP_001393620.1:p.Phe398Serfs
NP_001393621.1:p.Phe398Serfs
NP_001393622.1:p.Phe398Serfs
NP_001393623.1:p.Phe398Serfs
NP_001393624.1:p.Phe398Serfs
NP_001393625.1:p.Phe398Serfs
NP_001393626.1:p.Phe398Serfs
NP_001393627.1:p.Phe312Serfs
NP_066399.2:p.Phe846fs
LRG_487t1:c.2537del
LRG_487:g.30076del
LRG_487p1:p.Phe846Serfs
NC_000016.9:g.2124382del
NM_000548.3:c.2537delT
NR_176225.1:n.2687delT
NR_176226.1:n.2866delT
NR_176227.1:n.2866delT
NR_176228.1:n.2687delT
NR_176229.1:n.2647delT

Protein change:

F646fs

Molecular consequence:

NM_000548.5:c.2537del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001077183.3:c.2537del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001114382.3:c.2537del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001318827.2:c.2426del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001318829.2:c.2390del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001318831.2:c.1937del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001318832.2:c.2570del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001363528.2:c.2537del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370404.1:c.2537del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370405.1:c.2537del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406663.1:c.2537delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406664.1:c.2537delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406665.1:c.2537delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406667.1:c.2627delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406668.1:c.2627delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406670.1:c.2426delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406671.1:c.2525delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406673.1:c.2525delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406675.1:c.2390delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406676.1:c.2390delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406677.1:c.2480delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406678.1:c.2426delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406679.1:c.2390delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406680.1:c.1937delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406681.1:c.2075delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406682.1:c.1937delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406683.1:c.1937delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406684.1:c.1937delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406685.1:c.1937delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406686.1:c.1937delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406687.1:c.1937delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406688.1:c.1937delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406689.1:c.1193delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406690.1:c.1193delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406691.1:c.1193delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406692.1:c.1193delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406693.1:c.1193delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406694.1:c.1193delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406695.1:c.1193delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406696.1:c.1193delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406697.1:c.1193delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406698.1:c.935delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_021055.3:c.2537del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Tuberous sclerosis 2 (TSC2)
Identifiers:: MONDO: MONDO:0013199; MedGen: C1860707; Orphanet: 805; OMIM: 613254

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002573201	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 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

SCV002573201

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Sep 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	1	not provided	not provided	1	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 3billion, SCV002573201.1

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

Description

The variant is not observed in the gnomAD v2.1.1 dataset. Frameshift variant is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been shared with similarly affected sibling (3billion dataset) Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Nov 5, 2022

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