VCV001404342.13 - ClinVar

NM_001082486.2(ACD):c.862G>A (p.Glu288Lys)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Uncertain significance
Uncertain significance (2)

2 out of 3 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001082486.2(ACD):c.862G>A (p.Glu288Lys)

Variation ID: 1404342 Accession: VCV001404342.13

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 16q22.1 16: 67658330 (GRCh38) [ NCBI UCSC ] 16: 67692233 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Mar 28, 2022	Feb 15, 2026	Jan 14, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_001082486.2:c.862G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001075955.2:p.Glu288Lys	missense
NM_022914.3:c.853G>A	NP_075065.3:p.Glu285Lys	missense
NC_000016.10:g.67658330C>T
NC_000016.9:g.67692233C>T
NG_042874.1:g.7486G>A
NG_054728.1:g.18412C>T
LRG_1237:g.7486G>A
LRG_1237t1:c.862G>A	LRG_1237p1:p.Glu288Lys

... more HGVS ... less HGVS

Protein change

E288K, E285K

Other names

Canonical SPDI

NC_000016.10:67658329:C:T

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00020 (T)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.00001

Trans-Omics for Precision Medicine (TOPMed) 0.00001

Exome Aggregation Consortium (ExAC) 0.00002

The Genome Aggregation Database (gnomAD) 0.00003

The Genome Aggregation Database (gnomAD), exomes 0.00003

1000 Genomes Project 30x 0.00016

1000 Genomes Project 0.00020

Links

ClinGen: CA8114489 dbSNP: rs200298308 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
ACD		No evidence available	No evidence available	GRCh38 GRCh37	1263	1449

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Dyskeratosis congenita, autosomal dominant 6	Uncertain significance (1)	criteria provided, single submitter	Jan 14, 2026	RCV001901600.8
Inborn genetic diseases	Uncertain significance (1)	criteria provided, single submitter	Nov 3, 2025	RCV002441007.3
ACD-related disorder	Uncertain significance (1)	no assertion criteria provided	Oct 28, 2023	RCV003911089.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (Nov 03, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Inborn genetic diseases	Ambry Genetics Accession: SCV002746034.3 First in ClinVar: Nov 29, 2022 Last updated: Jan 11, 2026	Comment: show The c.1120G>A (p.E374K) alteration is located in exon 10 (coding exon 10) of the ACD gene. This alteration results from a G to A substitution at nucleotide position 1120, causing the glutamic acid (E) at amino acid position 374 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (Jan 14, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Dyskeratosis congenita, autosomal dominant 6	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002173217.5 First in ClinVar: Mar 28, 2022 Last updated: Feb 15, 2026	Comment: show This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 374 of the ACD protein (p.Glu374Lys). This variant is present in population databases (rs200298308, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with ACD-related conditions. ClinVar contains an entry for this variant (Variation ID: 1404342). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt ACD protein function with a negative predictive value of 80%. 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. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (Oct 28, 2023) N Not contributing to aggregate classification	no assertion criteria provided	ACD-related condition	PreventionGenetics, part of Exact Sciences Accession: SCV004727690.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: show The ACD c.1120G>A variant is predicted to result in the amino acid substitution p.Glu374Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.022% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-67692233-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

The c.1120G>A (p.E374K) alteration is located in exon 10 (coding exon 10) of the ACD gene. This alteration results from a G to A substitution at nucleotide position 1120, causing the glutamic acid (E) at amino acid position 374 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

Comment:

This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 374 of the ACD protein (p.Glu374Lys). This variant is present in population databases (rs200298308, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with ACD-related conditions. ClinVar contains an entry for this variant (Variation ID: 1404342). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt ACD protein function with a negative predictive value of 80%. 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.

Comment:

The ACD c.1120G>A variant is predicted to result in the amino acid substitution p.Glu374Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.022% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-67692233-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs200298308 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Feb 15, 2026