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NM_005359.6(SMAD4):c.1245_1248del (p.Asp415Glufs) AND Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Feb 9, 2024
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:
RCV003485541.2

Allele description [Variation Report for NM_005359.6(SMAD4):c.1245_1248del (p.Asp415Glufs)]

NM_005359.6(SMAD4):c.1245_1248del (p.Asp415Glufs)

Gene:
SMAD4:SMAD family member 4 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
18q21.2
Genomic location:
Preferred name:
NM_005359.6(SMAD4):c.1245_1248del (p.Asp415Glufs)
HGVS:
  • NC_000018.10:g.51067124_51067127del
  • NC_000018.9:g.48593491_48593494del
  • NG_013013.2:g.104085_104088del
  • NM_005359.6:c.1245_1248delMANE SELECT
  • NP_005350.1:p.Asp415fs
  • LRG_318t1:c.1245_1248del
  • LRG_318:g.104085_104088del
  • NC_000018.9:g.48593491_48593494del
  • NC_000018.9:g.48593494_48593497del
  • NC_000018.9:g.48593494_48593497delCAGA
  • NM_005359.5:c.1244_1247delACAG
  • NM_005359.5:c.1245_1248del
  • NM_005359.5:c.1245_1248delCAGA
  • p.Asp415Glufs*20
  • p.Asp415GlufsX20
  • p.D415EFS*20
  • p.D415EfsX20
Links:
OMIM: 600993.0005; dbSNP: rs80338965
NCBI 1000 Genomes Browser:
rs80338965
Molecular consequence:
  • NM_005359.6:c.1245_1248del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome (JPHT)
Synonyms:
JP/HHT SYNDROME; JUVENILE POLYPOSIS WITH HEREDITARY HEMORRHAGIC TELANGIECTASIA; POLYPOSIS, GENERALIZED JUVENILE, WITH PULMONARY ARTERIOVENOUS MALFORMATION; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008278; MedGen: C1832942; Orphanet: 2929; OMIM: 175050

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004022162deCODE genetics, Amgen
no assertion criteria provided
Likely pathogenic
(Jul 21, 2023) 		germlineresearch

SCV004932867Myriad Genetics, Inc.
criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))		Pathogenic
(Feb 9, 2024) 		unknownclinical testing

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
Icelandicgermlineyes2not providednot providednot providednot providedresearch

Details of each submission

From deCODE genetics, Amgen, SCV004022162.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Icelandic2not providednot providedresearchnot provided

Description

The variant NM_005359.6:c.1245_1248del (chr18:51067120) in SMAD4 was detected in 2 heterozygotes out of 58K WGS Icelanders (MAF= 0,002%). This variant has been reported in ClinVar previously as pathogenic. Based on ACMG criteria (PVS1, PM2) this variant classifies as likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided2not providednot providednot provided

From Myriad Genetics, Inc., SCV004932867.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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

Last Updated: May 26, 2024