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NM_000512.5(GALNS):c.422+2dup AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 10, 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:
RCV004800987.1

Allele description [Variation Report for NM_000512.5(GALNS):c.422+2dup]

NM_000512.5(GALNS):c.422+2dup

Gene:
GALNS:galactosamine (N-acetyl)-6-sulfatase [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
16q24.3
Genomic location:
Preferred name:
NM_000512.5(GALNS):c.422+2dup
HGVS:
  • NC_000016.10:g.88840990dup
  • NG_008667.1:g.20977dup
  • NM_000512.5:c.422+2dupMANE SELECT
  • NM_001323543.2:c.-134+2dup
  • NM_001323544.2:c.440+2dup
  • NC_000016.9:g.88907398dup
  • NM_000512.5:c.422+2dupTMANE SELECT
Links:
dbSNP: rs2143004586
NCBI 1000 Genomes Browser:
rs2143004586
Molecular consequence:
  • NM_000512.5:c.422+2dup - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001323543.2:c.-134+2dup - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001323544.2:c.440+2dup - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005422490Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(Oct 10, 2024) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Mucopolysaccharidosis IVA: correlation between genotype, phenotype and keratan sulfate levels.

Dũng VC, Tomatsu S, Montaño AM, Gottesman G, Bober MB, Mackenzie W, Maeda M, Mitchell GA, Suzuki Y, Orii T.

Mol Genet Metab. 2013 Sep-Oct;110(1-2):129-38. doi: 10.1016/j.ymgme.2013.06.008. Epub 2013 Jun 26.

PubMed [citation]
PMID:
23876334
PMCID:
PMC3779837

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005422490.1

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

Description

Variant summary: GALNS c.422+2dupT alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251020 control chromosomes (gnomAD). c.422+2dupT (also known as c.422+2_+3insT in the literature) has been reported in the literature in two siblings affected with severe Mucopolysaccharidosis Type IVA (Morquio Syndrome A) phenotype (example: Dung_2013). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 23876334). ClinVar contains an entry for this variant (Variation ID: 1048401). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

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

Last Updated: May 16, 2025