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NM_020975.6(RET):c.3222dup (p.Val1075fs) AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 12, 2018
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:
RCV001258057.1

Allele description [Variation Report for NM_020975.6(RET):c.3222dup (p.Val1075fs)]

NM_020975.6(RET):c.3222dup (p.Val1075fs)

Gene:
RET:ret proto-oncogene [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
10q11.21
Genomic location:
Preferred name:
NM_020975.6(RET):c.3222dup (p.Val1075fs)
HGVS:
  • NC_000010.11:g.43128146dup
  • NG_007489.1:g.56078dup
  • NM_020975.6:c.3222dupMANE SELECT
  • NP_066124.1:p.Val1075fs
  • LRG_518t1:c.3222dup
  • LRG_518:g.56078dup
  • NC_000010.10:g.43623593_43623594insT
  • NC_000010.10:g.43623594dup
  • NM_020975.4:c.3222dupT
Protein change:
V1075fs
Links:
dbSNP: rs1838374810
NCBI 1000 Genomes Browser:
rs1838374810
Molecular consequence:
  • NM_020975.6:c.3222dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
MULTIPLE ENDOCRINE NEOPLASIA, TYPE IIB (MEN2B)
Synonyms:
MEN IIB; NEUROMATA, MUCOSAL, WITH ENDOCRINE TUMORS; MULTIPLE ENDOCRINE NEOPLASIA, TYPE III; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008082; MeSH: D018814; MedGen: C0025269; Orphanet: 653; OMIM: 162300
Name:
MULTIPLE ENDOCRINE NEOPLASIA, TYPE IIA (MEN2A)
Synonyms:
Multiple endocrine neoplasia, type 2a; Sipple syndrome; MEN 2A; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008234; MeSH: D018813; MedGen: C0025268; Orphanet: 653; OMIM: 171400

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001434888Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Oct 12, 2018) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine, SCV001434888.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The c.3222dupT (p.Valu1075Cysfs*7) variant in the RET gene is predicted to introduce a premature translation termination codon. RET is an oncogene and cause multiple endocrine neoplasia through gain-of-function mechanism. Loss-of-function of RET has been reported to be associated with Hirschsprung disesae and possibly renal abnormalities (PMID: 18252215). The RET gene has a pLI score of 1, suggesting this gene is intolerant to loss-of-function variants. This variant has not been reported in the gnomAD database. Therefore, the c.3222dupT (p.Valu1075Cysfs*7) variant in the RET gene is classified as likely pathogenic for Hirschsprung disease, but a variant of unknown significance for MEN type 2A/B and Familial Medullary Thyroid cancer.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 20, 2024