NM_001104631.2(PDE4D):c.998T>C (p.Ile333Thr) AND Acrodysostosis 2 with or without hormone resistance

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 23, 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:: RCV003153219.1

Allele description [Variation Report for NM_001104631.2(PDE4D):c.998T>C (p.Ile333Thr)]

NM_001104631.2(PDE4D):c.998T>C (p.Ile333Thr)

Gene:

PDE4D:phosphodiesterase 4D [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q11.2

Genomic location:

Preferred name:

NM_001104631.2(PDE4D):c.998T>C (p.Ile333Thr)

HGVS:

NC_000005.10:g.58993389A>G
NG_027957.2:g.1535941T>C
NM_001104631.2:c.998T>CMANE SELECT
NM_001165899.2:c.815T>C
NM_001197218.2:c.806T>C
NM_001197219.2:c.632T>C
NM_001197220.2:c.608T>C
NM_001197221.2:c.92T>C
NM_001197222.2:c.326T>C
NM_001197223.2:c.125T>C
NM_001349241.2:c.785T>C
NM_001349242.2:c.668T>C
NM_001349243.2:c.230T>C
NM_001364599.1:c.815T>C
NM_001364603.1:c.92T>C
NM_001364604.1:c.230T>C
NM_006203.5:c.590T>C
NP_001098101.1:p.Ile333Thr
NP_001159371.1:p.Ile272Thr
NP_001184147.1:p.Ile269Thr
NP_001184148.1:p.Ile211Thr
NP_001184149.1:p.Ile203Thr
NP_001184150.1:p.Ile31Thr
NP_001184151.1:p.Ile109Thr
NP_001184152.1:p.Ile42Thr
NP_001336170.1:p.Ile262Thr
NP_001336171.1:p.Ile223Thr
NP_001336172.1:p.Ile77Thr
NP_001351528.1:p.Ile272Thr
NP_001351532.1:p.Ile31Thr
NP_001351533.1:p.Ile77Thr
NP_006194.2:p.Ile197Thr
NC_000005.9:g.58289216A>G

Protein change:

I109T

Molecular consequence:

NM_001104631.2:c.998T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001165899.2:c.815T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001197218.2:c.806T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001197219.2:c.632T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001197220.2:c.608T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001197221.2:c.92T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001197222.2:c.326T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001197223.2:c.125T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001349241.2:c.785T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001349242.2:c.668T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001349243.2:c.230T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001364599.1:c.815T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001364603.1:c.92T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001364604.1:c.230T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_006203.5:c.590T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Acrodysostosis 2 with or without hormone resistance
Synonyms:: ACRODYSOSTOSIS 2 WITH HORMONE RESISTANCE; ACRODYSOSTOSIS 2 WITHOUT HORMONE RESISTANCE
Identifiers:: MONDO: MONDO:0013822; MedGen: C3553250; Orphanet: 280651; OMIM: 614613

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003842122	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 23, 2023)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30006632, 25044890, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003842122

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 23, 2023)

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Expanding the phenotypic spectrum of variants in PDE4D/PRKAR1A: from acrodysostosis to acroscyphodysplasia.

Michot C, Le Goff C, Blair E, Blanchet P, Capri Y, Gilbert-Dussardier B, Goldenberg A, Henderson A, Isidor B, Kayserili H, Kinning E, Le Merrer M, Lyonnet S, Odent S, Simsek-Kiper PO, Quelin C, Savarirayan R, Simon M, Splitt M, Verhagen JMA, Verloes A, Munnich A, et al.

Eur J Hum Genet. 2018 Nov;26(11):1611-1622. doi: 10.1038/s41431-018-0135-1. Epub 2018 Jul 13.

PubMed [citation]

PMID:: 30006632
PMCID:: PMC6189044

Acroscyphodysplasia as a phenotypic variation of pseudohypoparathyroidism and acrodysostosis type 2.

Mitsui T, Kim OH, Hall CM, Offiah A, Johnson D, Jin DK, Toh TH, Soneda S, Keino D, Matsubayashi S, Ishii T, Nishimura G, Hasegawa T.

Am J Med Genet A. 2014 Oct;164A(10):2529-34. doi: 10.1002/ajmg.a.36669. Epub 2014 Jul 10.

PubMed [citation]

PMID:: 25044890

See all PubMed Citations (3)

Details of each submission

From 3billion, SCV003842122.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.91; 3Cnet: 0.11). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with PDE4D related disorder, and reported as de novo in at least two similarly affected unrelated individuals (PMID: 25044890). A different missense change at the same codon (p.Ile333Val) has been reported to be associated with PDE4D related disorder (PMID: 30006632). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 5, 2024

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