U.S. flag

An official website of the United States government

NM_001042492.3(NF1):c.8456G>A (p.Ser2819Asn) AND Neurofibromatosis, type 1

Germline classification:
Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:
May 15, 2023
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:
RCV000543184.20

Allele description [Variation Report for NM_001042492.3(NF1):c.8456G>A (p.Ser2819Asn)]

NM_001042492.3(NF1):c.8456G>A (p.Ser2819Asn)

Gene:
NF1:neurofibromin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q11.2
Genomic location:
Preferred name:
NM_001042492.3(NF1):c.8456G>A (p.Ser2819Asn)
HGVS:
  • NC_000017.11:g.31374091G>A
  • NG_009018.1:g.284115G>A
  • NM_000267.3:c.8393G>A
  • NM_001042492.3:c.8456G>AMANE SELECT
  • NP_000258.1:p.Ser2798Asn
  • NP_001035957.1:p.Ser2819Asn
  • NP_001035957.1:p.Ser2819Asn
  • LRG_214t1:c.8393G>A
  • LRG_214t2:c.8456G>A
  • LRG_214:g.284115G>A
  • LRG_214p1:p.Ser2798Asn
  • LRG_214p2:p.Ser2819Asn
  • NC_000017.10:g.29701109G>A
  • NM_001042492.2:c.8456G>A
  • NM_001042492.3:c.8456G>A
Protein change:
S2798N
Links:
dbSNP: rs934837854
NCBI 1000 Genomes Browser:
rs934837854
Molecular consequence:
  • NM_000267.3:c.8393G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001042492.3:c.8456G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Neurofibromatosis, type 1 (NF1)
Synonyms:
NEUROFIBROMATOSIS, TYPE I; Recklinghausen's disease; Von Recklinghausen disease; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0018975; MedGen: C0027831; Orphanet: 636; OMIM: 162200

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000628817Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Likely benign
(May 15, 2023)
germlineclinical testing

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

SCV002526085St. Jude Molecular Pathology, St. Jude Children's Research Hospital
criteria provided, single submitter

(St. Jude Assertion Criteria 2020)
Uncertain significance
(Dec 21, 2021)
germlineclinical testing

Citation Link,

SCV002561524Genome-Nilou Lab
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Mar 15, 2022)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000628817.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From St. Jude Molecular Pathology, St. Jude Children's Research Hospital, SCV002526085.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The NF1 c.8393G>A (p.Ser2798Asn) missense change has a maximum subpopulation frequency of 0.011% in gnomAD v2.1.1 (PM2_supporitng; https://gnomad.broadinstitute.org/variant/17-29701109-G-A). In silico tools are not in agreement about the effect of this variant on protein function, but to our knowledge these predictions have not been confirmed by functional assays. This variant occurs in a gene where missense variants are more likely to be damaging based on methods described by Lek et al. (PP2; PMID: 27535533). To our knowledge, this variant has not been reported in individuals with Neurofibromatosis type 1. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PM2_supporting, PP2.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Genome-Nilou Lab, SCV002561524.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 8, 2024