NM_024598.4(USB1):c.623A>G (p.His208Arg) AND Poikiloderma with neutropenia

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: May 25, 2020
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:: RCV000599396.3

Allele description [Variation Report for NM_024598.4(USB1):c.623A>G (p.His208Arg)]

NM_024598.4(USB1):c.623A>G (p.His208Arg)

Gene:

USB1:U6 snRNA biogenesis phosphodiesterase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q21

Genomic location:

Preferred name:

NM_024598.4(USB1):c.623A>G (p.His208Arg)

HGVS:

NC_000016.10:g.58018985A>G
NG_027698.1:g.22613A>G
NM_001195302.2:c.569A>G
NM_001330568.2:c.470A>G
NM_024598.4:c.623A>GMANE SELECT
NP_001182231.1:p.His190Arg
NP_001317497.1:p.His157Arg
NP_078874.2:p.(His208Arg)
NP_078874.2:p.His208Arg
NP_078874.2:p.His208Arg
LRG_352t1:c.623A>G
LRG_352t1:c.623A>G
LRG_352:g.22613A>G
LRG_352p1:p.(His208Arg)
LRG_352p1:p.His208Arg
NC_000016.9:g.58052889A>G
NM_024598.3:c.623A>G

Protein change:

H157R

Links:

dbSNP: rs1249059283

NCBI 1000 Genomes Browser:

rs1249059283

Molecular consequence:

NM_001195302.2:c.569A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330568.2:c.470A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_024598.4:c.623A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Poikiloderma with neutropenia (PN)
Synonyms:: Poikiloderma with neutropenia Clericuzio type
Identifiers:: MONDO: MONDO:0011405; MedGen: C1858723; Orphanet: 221046; OMIM: 604173

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000700235	GeneReviews	no classification provided	not provided	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002769442	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 25, 2020)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23190533, 27612988, 29982244, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000700235

GeneReviews

no classification provided

not provided

germline

literature only

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

SCV002769442

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 25, 2020)

germline

clinical testing

PubMed (4)
[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	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Poikiloderma with Neutropenia.

Wang L, Clericuzio C, Larizza L, Concolino D.

2017 Oct 26 [updated 2024 Feb 22]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(®) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024.

PubMed [citation]

PMID:: 29072891

Aberrant 3' oligoadenylation of spliceosomal U6 small nuclear RNA in poikiloderma with neutropenia.

Hilcenko C, Simpson PJ, Finch AJ, Bowler FR, Churcher MJ, Jin L, Packman LC, Shlien A, Campbell P, Kirwan M, Dokal I, Warren AJ.

Blood. 2013 Feb 7;121(6):1028-38. doi: 10.1182/blood-2012-10-461491. Epub 2012 Nov 27.

PubMed [citation]

PMID:: 23190533

See all PubMed Citations (5)

Details of each submission

From GeneReviews, SCV000700235.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

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

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002769442.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as LIKELY PATHOGENIC. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0106 - This gene is known to be associated with autosomal recessive disease. (N) 0200 - Variant is predicted to result in a missense amino acid change from a histidine to an arginine (exon 6). (N) 0252 - Variant is homozygous. (N) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (2 heterozygotes, 0 homozygotes) (P) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (1 heterozygote, 0 homozygotes). (N) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools and highly conserved with a minor amino acid change. (P) 0601 - Variant affects a residue within the catalytic site, which has been shown to be involved in digesting RNA substrates (PMID: 23190533). (P) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0802 - Moderate previous evidence of pathogenicity in unrelated individuals. (PMID: 27612988, 29982244) (P) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign

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

Last Updated: Oct 8, 2024

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