NM_001130823.3(DNMT1):c.4876G>A (p.Glu1626Lys) AND not provided

Germline classification:: Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:: Dec 22, 2020
Review status:: criteria provided, conflicting classifications

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:: RCV000757172.15

Allele description [Variation Report for NM_001130823.3(DNMT1):c.4876G>A (p.Glu1626Lys)]

NM_001130823.3(DNMT1):c.4876G>A (p.Glu1626Lys)

Gene:

DNMT1:DNA methyltransferase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_001130823.3(DNMT1):c.4876G>A (p.Glu1626Lys)

HGVS:

NC_000019.10:g.10133690C>T
NG_028016.3:g.102597G>A
NM_001130823.3:c.4876G>AMANE SELECT
NM_001318730.2:c.4837G>A
NM_001318731.2:c.4513G>A
NM_001379.4:c.4828G>A
NP_001124295.1:p.Glu1626Lys
NP_001305659.1:p.Glu1613Lys
NP_001305660.1:p.Glu1505Lys
NP_001370.1:p.Glu1610Lys
LRG_362t1:c.4876G>A
LRG_362:g.102597G>A
NC_000019.9:g.10244366C>T
NM_001130823.1:c.4876G>A
NM_001379.2:c.4828G>A

Protein change:

E1505K

Links:

dbSNP: rs201774098

NCBI 1000 Genomes Browser:

rs201774098

Molecular consequence:

NM_001130823.3:c.4876G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318730.2:c.4837G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318731.2:c.4513G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001379.4:c.4828G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000293365	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely benign (Dec 22, 2020)	germline	clinical testing	Citation Link,
SCV000885307	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Uncertain significance (Feb 2, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000293365

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely benign
(Dec 22, 2020)

germline

clinical testing

Citation Link,

SCV000885307

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)

Uncertain significance
(Feb 2, 2018)

germline

clinical testing

Citation Link

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	clinical testing

Details of each submission

From GeneDx, SCV000293365.9

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

#	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

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000885307.1

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

Description

The DNMT1 c.4876G>A; p.Glu1626Lys variant (rs201774098), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.02% (identified on 45 out of 211,492 chromosomes) and is classified as a variant of uncertain significance in ClinVar (ID: 246060). The glutamic acid at position 1626 is moderately conserved, considering 12 species and computational analyses of the effects of the p.Glu1626Lys variant on protein structure and function do not predict a deleterious effect (SIFT: tolerated, MutationTaster: polymorphism, PolyPhen-2: benign). Based on the available information, the clinical significance of the p.Glu1626Lys variant cannot be determined with certainty.

#	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: Jan 19, 2025

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