NM_001098668.4(SFTPA2):c.697T>A (p.Trp233Arg) AND Interstitial lung disease 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 19, 2021
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV001784080.1

Allele description [Variation Report for NM_001098668.4(SFTPA2):c.697T>A (p.Trp233Arg)]

NM_001098668.4(SFTPA2):c.697T>A (p.Trp233Arg)

Gene:

SFTPA2:surfactant protein A2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q22.3

Genomic location:

Preferred name:

NM_001098668.4(SFTPA2):c.697T>A (p.Trp233Arg)

HGVS:

NC_000010.11:g.79557259A>T
NG_013046.1:g.8149T>A
NM_001098668.4:c.697T>AMANE SELECT
NM_001320813.2:c.697T>A
NM_001320814.1:c.727T>A
NP_001092138.1:p.Trp233Arg
NP_001307742.1:p.Trp233Arg
NP_001307743.1:p.Trp243Arg
NC_000010.10:g.81317015A>T
NM_001098668.2:c.697T>A

Protein change:

W233R; TRP233ARG

Links:

OMIM: 178642.0005; dbSNP: rs2132045183

NCBI 1000 Genomes Browser:

rs2132045183

Molecular consequence:

NM_001098668.4:c.697T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001320813.2:c.697T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001320814.1:c.727T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Interstitial lung disease 2 (ILD2)
Synonyms:: Fibrosing alveolitis, cryptogenic; Familial idiopathic pulmonary fibrosis; Fibrocystic pulmonary dysplasia
Identifiers:: MONDO: MONDO:0800029; MedGen: C5561926; Orphanet: 2032; Orphanet: 79126; OMIM: 178500

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002025262	OMIM	no assertion criteria provided	Pathogenic (Nov 19, 2021)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002025262

OMIM

no assertion criteria provided

Pathogenic
(Nov 19, 2021)

germline

literature only

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Functional assessment and phenotypic heterogeneity of SFTPA1 and SFTPA2 mutations in interstitial lung diseases and lung cancer.

Legendre M, Butt A, Borie R, Debray MP, Bouvry D, Filhol-Blin E, Desroziers T, Nau V, Copin B, Dastot-Le Moal F, Héry M, Duquesnoy P, Allou N, Bergeron A, Bermudez J, Cazes A, Chene AL, Cottin V, Crestani B, Dalphin JC, Dombret C, Doray B, et al.

Eur Respir J. 2020 Dec 24;56(6). doi:pii: 2002806. 10.1183/13993003.02806-2020. Print 2020 Dec.

PubMed [citation]

PMID:: 32855221

Details of each submission

From OMIM, SCV002025262.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a mother and son (family 8) with interstitial lung disease-2 (ILD2; 178500), Legendre et al. (2020) identified a heterozygous c.697T-A transversion (c.697T-A, NM_001098668.2) in exon 6 of the SFTPA2 gene, resulting in a trp233-to-arg (W233R) substitution in the CRD domain. The mutation, which was found by direct sequencing, was not present in the gnomAD database. In vitro functional expression studies in HEK293T cells transfected with the mutation showed normal protein expression with decreased secretion of SFTPA2 compared to controls. Abnormal cytoplasmic retention of mutant SFTPA2 in the alveolar epithelium was considered to contribute to pathogenicity. There was a significant family history of similar lung disease, including lung cancer, but DNA from affected family members was not available for segregation studies.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 24, 2023

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