NM_000484.4(APP):c.2212-11_2212-10del AND not specified

Germline classification:: Benign (2 submissions)
Last evaluated:: Sep 30, 2024
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:: RCV001579410.3

Allele description [Variation Report for NM_000484.4(APP):c.2212-11_2212-10del]

NM_000484.4(APP):c.2212-11_2212-10del

Gene:

APP:amyloid beta precursor protein [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

21q21.3

Genomic location:

Preferred name:

NM_000484.4(APP):c.2212-11_2212-10del

HGVS:

NC_000021.9:g.25881781_25881782del
NG_007376.2:g.294347_294348del
NM_000484.4:c.2212-11_2212-10delMANE SELECT
NM_001136016.3:c.2140-11_2140-10del
NM_001136129.3:c.1819-11_1819-10del
NM_001136130.3:c.2044-11_2044-10del
NM_001136131.3:c.1882-11_1882-10del
NM_001204301.2:c.2158-11_2158-10del
NM_001204302.2:c.2101-11_2101-10del
NM_001204303.2:c.1933-11_1933-10del
NM_001385253.1:c.2044-11_2044-10del
NM_201413.3:c.2155-11_2155-10del
NM_201414.3:c.1987-11_1987-10del
NC_000021.8:g.27254092_27254093del
NM_000484.3:c.2212-11_2212-10del
NM_000484.3:c.2212-11_2212-10delTT
NM_000484.4:c.2212-11_2212-10delTTMANE SELECT

Links:

dbSNP: rs112965435

NCBI 1000 Genomes Browser:

rs112965435

Molecular consequence:

NM_000484.4:c.2212-11_2212-10del - intron variant - [Sequence Ontology: SO:0001627]
NM_001136016.3:c.2140-11_2140-10del - intron variant - [Sequence Ontology: SO:0001627]
NM_001136129.3:c.1819-11_1819-10del - intron variant - [Sequence Ontology: SO:0001627]
NM_001136130.3:c.2044-11_2044-10del - intron variant - [Sequence Ontology: SO:0001627]
NM_001136131.3:c.1882-11_1882-10del - intron variant - [Sequence Ontology: SO:0001627]
NM_001204301.2:c.2158-11_2158-10del - intron variant - [Sequence Ontology: SO:0001627]
NM_001204302.2:c.2101-11_2101-10del - intron variant - [Sequence Ontology: SO:0001627]
NM_001204303.2:c.1933-11_1933-10del - intron variant - [Sequence Ontology: SO:0001627]
NM_001385253.1:c.2044-11_2044-10del - intron variant - [Sequence Ontology: SO:0001627]
NM_201413.3:c.2155-11_2155-10del - intron variant - [Sequence Ontology: SO:0001627]
NM_201414.3:c.1987-11_1987-10del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001807131	Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus	no assertion criteria provided	Benign	germline	clinical testing
SCV004028726	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Sep 30, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001807131

Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus

no assertion criteria provided

Benign

germline

clinical testing

SCV004028726

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Benign
(Sep 30, 2024)

germline

clinical testing

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

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

Citations

PubMed

Rare variants in β-Amyloid precursor protein (APP) and Parkinson's disease.

Schulte EC, Fukumori A, Mollenhauer B, Hor H, Arzberger T, Perneczky R, Kurz A, Diehl-Schmid J, Hüll M, Lichtner P, Eckstein G, Zimprich A, Haubenberger D, Pirker W, Brücke T, Bereznai B, Molnar MJ, Lorenzo-Betancor O, Pastor P, Peters A, Gieger C, Estivill X, et al.

Eur J Hum Genet. 2015 Oct;23(10):1328-33. doi: 10.1038/ejhg.2014.300. Epub 2015 Jan 21.

PubMed [citation]

PMID:: 25604855
PMCID:: PMC4592093

Details of each submission

From Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus, SCV001807131.1

#	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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004028726.2

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

Description

Variant summary: APP c.2212-11_2212-10delTT alters a nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00079 in 250828 control chromosomes, predominantly at a frequency of 0.0055 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database exceeds the estimated maximal expected allele frequency for a pathogenic variant in APP causing Alzheimer Disease phenotype. c.2212-11_2212-10delTT has been reported in the literature in individuals affected with Alzheimer Disease. These report(s) do not provide unequivocal conclusions about association of the variant with Alzheimer Disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 585433). Based on the evidence outlined above, the variant was classified as benign.

#	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: May 16, 2025

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