NM_000032.5(ALAS2):c.1706_1709del (p.Glu569fs) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 25, 2023
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:
RCV001851788.11

Allele description [Variation Report for NM_000032.5(ALAS2):c.1706_1709del (p.Glu569fs)]

NM_000032.5(ALAS2):c.1706_1709del (p.Glu569fs)

Gene:
ALAS2:5'-aminolevulinate synthase 2 [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
Xp11.21
Genomic location:
Preferred name:
NM_000032.5(ALAS2):c.1706_1709del (p.Glu569fs)
HGVS:
  • NC_000023.11:g.55009237CTCA[1]
  • NG_008983.1:g.26823AGTG[1]
  • NG_008983.1:g.26827_26830del
  • NG_012568.1:g.13891CTCA[1]
  • NM_000032.5:c.1706_1709delMANE SELECT
  • NM_001037967.4:c.1595_1598del
  • NM_001037968.4:c.1667_1670del
  • NP_000023.2:p.Glu569fs
  • NP_001033056.1:p.Glu532fs
  • NP_001033057.1:p.Glu556fs
  • LRG_1163t1:c.1706_1709del
  • LRG_1163:g.26823AGTG[1]
  • LRG_1163p1:p.Glu569fs
  • NC_000023.10:g.55035668_55035671del
  • NC_000023.10:g.55035670CTCA[1]
  • NG_008983.1:g.26827_26830del
  • NM_000032.4:c.1706_1709delAGTG
Protein change:
E532fs
Links:
OMIM: 301300.0015; dbSNP: rs387906472
NCBI 1000 Genomes Browser:
rs387906472
Molecular consequence:
  • NM_000032.5:c.1706_1709del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001037967.4:c.1595_1598del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001037968.4:c.1667_1670del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002131163Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 25, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Molecular and functional analysis of the C-terminal region of human erythroid-specific 5-aminolevulinic synthase associated with X-linked dominant protoporphyria (XLDPP).

Ducamp S, Schneider-Yin X, de Rooij F, Clayton J, Fratz EJ, Rudd A, Ostapowicz G, Varigos G, Lefebvre T, Deybach JC, Gouya L, Wilson P, Ferreira GC, Minder EI, Puy H.

Hum Mol Genet. 2013 Apr 1;22(7):1280-8. doi: 10.1093/hmg/dds531. Epub 2012 Dec 20.

PubMed [citation]
PMID:
23263862

C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload.

Whatley SD, Ducamp S, Gouya L, Grandchamp B, Beaumont C, Badminton MN, Elder GH, Holme SA, Anstey AV, Parker M, Corrigall AV, Meissner PN, Hift RJ, Marsden JT, Ma Y, Mieli-Vergani G, Deybach JC, Puy H.

Am J Hum Genet. 2008 Sep;83(3):408-14. doi: 10.1016/j.ajhg.2008.08.003. Epub 2008 Sep 4.

PubMed [citation]
PMID:
18760763
PMCID:
PMC2556430
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV002131163.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this frameshift affects ALAS2 function (PMID: 23263862). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 10482). This frameshift has been observed in individual(s) with X-linked dominant erythropoietic protoporphyria (PMID: 18760763). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the ALAS2 gene (p.Glu569Glyfs*24). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 19 amino acid(s) of the ALAS2 protein and extend the protein by 4 additional amino acid residues.

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

Last Updated: May 19, 2024