NM_022836.4(DCLRE1B):c.689A>G (p.His230Arg) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 28, 2019
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:: RCV001202897.7

Allele description [Variation Report for NM_022836.4(DCLRE1B):c.689A>G (p.His230Arg)]

NM_022836.4(DCLRE1B):c.689A>G (p.His230Arg)

Gene:

DCLRE1B:DNA cross-link repair 1B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p13.2

Genomic location:

Preferred name:

NM_022836.4(DCLRE1B):c.689A>G (p.His230Arg)

HGVS:

NC_000001.11:g.113911281A>G
NG_057565.1:g.11663A>G
NM_001319946.2:c.311A>G
NM_001319947.2:c.311A>G
NM_001363690.2:c.689A>G
NM_001363691.2:c.311A>G
NM_022836.4:c.689A>GMANE SELECT
NP_001306875.1:p.His104Arg
NP_001306876.1:p.His104Arg
NP_001350619.1:p.His230Arg
NP_001350620.1:p.His104Arg
NP_073747.1:p.His230Arg
LRG_1219t1:c.689A>G
LRG_1219:g.11663A>G
LRG_1219p1:p.His230Arg
NC_000001.10:g.114453903A>G
NM_022836.3:c.689A>G

Protein change:

H104R

Links:

dbSNP: rs755456896

NCBI 1000 Genomes Browser:

rs755456896

Molecular consequence:

NM_001319946.2:c.311A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001319947.2:c.311A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001363690.2:c.689A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001363691.2:c.311A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_022836.4:c.689A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hoyeraal-Hreidarsson syndrome (HHS)
Synonyms:: Cerebellar hypoplasia with pancytopenia; Growth retardation prenatal with progressive pancytopenia and cerebellar hypoplasia
Identifiers:: MONDO: MONDO:0018045; MedGen: C1846142

Name:: Autosomal recessive dyskeratosis congenita
Identifiers:: MedGen: C3502105

Recent activity

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PREDICTED: Homo sapiens leukocyte receptor cluster member 8 (LENG8), transcript ...
PREDICTED: Homo sapiens leukocyte receptor cluster member 8 (LENG8), transcript variant X1, mRNA
gi|2217319093|ref|XM_005278250.6|

Nucleotide
SRX19778770 (1)
SRA
PREDICTED: Benincasa hispida thioredoxin H-type-like (LOC120076451), mRNA
PREDICTED: Benincasa hispida thioredoxin H-type-like (LOC120076451), mRNA
gi|1955856271|ref|XM_039030283.1|

Nucleotide
Component(Core) Links for Nucleotide (Select 1201920836) (9)
Nucleotide
OMIM Links for Nucleotide (Select 511855) (1)
OMIM

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001374031	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 28, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001374031

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 28, 2019)

germline

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001374031.5

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

Description

This variant has not been reported in the literature in individuals with DCLRE1B-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is present in population databases (rs755456896, ExAC 0.004%). This sequence change replaces histidine with arginine at codon 230 of the DCLRE1B protein (p.His230Arg). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and arginine.

#	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

Last Updated: Sep 29, 2024

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