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NM_014159.7(SETD2):c.7355C>T (p.Ser2452Leu) AND Luscan-Lumish syndrome

Germline classification:
Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:
Nov 27, 2023
Review status:
criteria provided, conflicting classifications
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:
RCV001229267.5

Allele description [Variation Report for NM_014159.7(SETD2):c.7355C>T (p.Ser2452Leu)]

NM_014159.7(SETD2):c.7355C>T (p.Ser2452Leu)

Gene:
SETD2:SET domain containing 2, histone lysine methyltransferase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p21.31
Genomic location:
Preferred name:
NM_014159.7(SETD2):c.7355C>T (p.Ser2452Leu)
HGVS:
  • NC_000003.12:g.47019836G>A
  • NG_032091.1:g.149142C>T
  • NM_001349370.3:c.7223C>T
  • NM_014159.7:c.7355C>TMANE SELECT
  • NP_001336299.1:p.Ser2408Leu
  • NP_054878.5:p.Ser2452Leu
  • LRG_775t1:c.7355C>T
  • LRG_775:g.149142C>T
  • NC_000003.11:g.47061326G>A
  • NM_014159.6:c.7355C>T
  • NR_146158.3:n.7712C>T
Protein change:
S2408L
Links:
dbSNP: rs775780402
NCBI 1000 Genomes Browser:
rs775780402
Molecular consequence:
  • NM_001349370.3:c.7223C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_014159.7:c.7355C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_146158.3:n.7712C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
1

Condition(s)

Name:
Luscan-Lumish syndrome
Identifiers:
MONDO: MONDO:0014791; MedGen: C4085873; OMIM: 616831

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001401708Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Likely benign
(Nov 27, 2023)
germlineclinical testing

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

SCV002025662New York Genome Center - CSER-NYCKidSeq
criteria provided, single submitter

(NYGC Assertion Criteria 2020)
Uncertain significance
(Apr 25, 2020)
germlineclinical testing

Citation Link,

SCV002555331Genome-Nilou Lab
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Mar 15, 2022)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing

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. doi: 10.1038/s41436-019-0624-9.

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, SCV001401708.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From New York Genome Center - CSER-NYCKidSeq, SCV002025662.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The p.Ser2452Leu variant identified in SETD2 has not been reported in affected individuals in the literature. The variant has 0.0000278 allele frequency in gnomAD database (7 out of 251,388 heterozygous alleles) indicating it is a rare allele in general population. The variant affects an evolutionarily conserved residue and is predicted deleterious by multiple in silico prediction tools. Based on the current evidence, the p.Ser2452Leu variant in the SETD2 gene is assessed as a variant of uncertain significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

From Genome-Nilou Lab, SCV002555331.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 1, 2024