chr4-174490230-GC-AT

Variant names:

• chr4-174490230-GC-AT
• rs371061653
• NM_000860.6:c.*1725_*1726delGCinsAT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000860.6(HPGD):​c.*1725_*1726delGCinsAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HPGD NM_000860.6 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: -0.105
• Publications: 0 publications found

Genes affected

HPGD (HGNC:5154): (15-hydroxyprostaglandin dehydrogenase) This gene encodes a member of the short-chain nonmetalloenzyme alcohol dehydrogenase protein family. The encoded enzyme is responsible for the metabolism of prostaglandins, which function in a variety of physiologic and cellular processes such as inflammation. Mutations in this gene result in primary autosomal recessive hypertrophic osteoarthropathy and cranioosteoarthropathy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

HPGD Gene-Disease associations (from GenCC):

• hypertrophic osteoarthropathy, primary, autosomal recessive, 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
• cranio-osteoarthropathy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• pachydermoperiostosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• isolated congenital digital clubbing

  Inheritance: Unknown, AD, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPGD	NM_000860.6	c.*1725_*1726delGCinsAT		3_prime_UTR_variant	Exon 7 of 7	ENST00000296522.11	NP_000851.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPGD	ENST00000296522.11	c.*1725_*1726delGCinsAT		3_prime_UTR_variant	Exon 7 of 7	1	NM_000860.6	ENSP00000296522.6
HPGD	ENST00000542498.5	c.*1853_*1854delGCinsAT		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000443644.1
HPGD	ENST00000541923.5	c.*1725_*1726delGCinsAT		3_prime_UTR_variant	Exon 6 of 6	2		ENSP00000438017.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

Hypertrophic osteoarthropathy, primary, autosomal recessive, 1 Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Isolated congenital digital clubbing Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.10

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs371061653; hg19: chr4-175411381;