NM_003105.6(SORL1):c.2416G>A (p.Asp806Asn) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 14, 2023
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:: RCV003058358.2

Allele description [Variation Report for NM_003105.6(SORL1):c.2416G>A (p.Asp806Asn)]

NM_003105.6(SORL1):c.2416G>A (p.Asp806Asn)

Genes:

LOC114803469:SORL1 eExon liver enhancer [Gene]
SORL1:sortilin related receptor 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q24.1

Genomic location:

Preferred name:

NM_003105.6(SORL1):c.2416G>A (p.Asp806Asn)

HGVS:

NC_000011.10:g.121554086G>A
NG_023313.2:g.106774G>A
NG_064645.1:g.419G>A
NM_003105.6:c.2416G>AMANE SELECT
NP_003096.2:p.Asp806Asn
NC_000011.9:g.121424795G>A
NG_023313.1:g.106835G>A

Protein change:

D806N

Molecular consequence:

NM_003105.6:c.2416G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003441052	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 14, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 26303663, 28789839, 34922638, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003441052

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 14, 2023)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

SORL1 rare variants: a major risk factor for familial early-onset Alzheimer's disease.

Nicolas G, Charbonnier C, Wallon D, Quenez O, Bellenguez C, Grenier-Boley B, Rousseau S, Richard AC, Rovelet-Lecrux A, Le Guennec K, Bacq D, Garnier JG, Olaso R, Boland A, Meyer V, Deleuze JF, Amouyel P, Munter HM, Bourque G, Lathrop M, Frebourg T, Redon R, et al.

Mol Psychiatry. 2016 Jun;21(6):831-6. doi: 10.1038/mp.2015.121. Epub 2015 Aug 25.

PubMed [citation]

PMID:: 26303663

Contribution to Alzheimer's disease risk of rare variants in TREM2, SORL1, and ABCA7 in 1779 cases and 1273 controls.

Bellenguez C, Charbonnier C, Grenier-Boley B, Quenez O, Le Guennec K, Nicolas G, Chauhan G, Wallon D, Rousseau S, Richard AC, Boland A, Bourque G, Munter HM, Olaso R, Meyer V, Rollin-Sillaire A, Pasquier F, Letenneur L, Redon R, Dartigues JF, Tzourio C, Frebourg T, et al.

Neurobiol Aging. 2017 Nov;59:220.e1-220.e9. doi: 10.1016/j.neurobiolaging.2017.07.001. Epub 2017 Jul 14.

PubMed [citation]

PMID:: 28789839

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV003441052.2

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

Description

This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 806 of the SORL1 protein (p.Asp806Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Alzheimer disease (PMID: 26303663, 28789839). ClinVar contains an entry for this variant (Variation ID: 2137277). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects SORL1 function (PMID: 34922638). 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.

#	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: Feb 20, 2024

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