NM_001098668.4(SFTPA2):c.532G>A (p.Val178Met) AND Interstitial lung disease 2

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 1, 2022
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:: RCV001780219.2

Allele description [Variation Report for NM_001098668.4(SFTPA2):c.532G>A (p.Val178Met)]

NM_001098668.4(SFTPA2):c.532G>A (p.Val178Met)

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.532G>A (p.Val178Met)

Other names:

SFTPA2, VAL178MET (rs371035540)

HGVS:

NC_000010.11:g.79557424C>T
NG_013046.1:g.7984G>A
NM_001098668.4:c.532G>AMANE SELECT
NM_001320813.2:c.532G>A
NM_001320814.1:c.562G>A
NP_001092138.1:p.Val178Met
NP_001307742.1:p.Val178Met
NP_001307743.1:p.Val188Met
NC_000010.10:g.81317180C>T
NM_001098668.2:c.532G>A

Protein change:

V178M; VAL178MET

Links:

OMIM: 178642.0004; dbSNP: rs371035540

NCBI 1000 Genomes Browser:

rs371035540

Molecular consequence:

NM_001098668.4:c.532G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001320813.2:c.532G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001320814.1:c.562G>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
SCV002016364	OMIM	no assertion criteria provided	Pathogenic (Nov 18, 2021)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002573690	Alder lab, University of Pittsburgh	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 1, 2022)	germline	research	PubMed (3) [See all records that cite these PMIDs] 25553246, 32855221, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002016364

OMIM

no assertion criteria provided

Pathogenic
(Nov 18, 2021)

germline

literature only

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

SCV002573690

Alder lab, University of Pittsburgh

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 1, 2022)

germline

research

PubMed (3)
[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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	yes	2	not provided	not provided	not provided	not provided	research

Citations

PubMed

Sequencing of idiopathic pulmonary fibrosis-related genes reveals independent single gene associations.

Coghlan MA, Shifren A, Huang HJ, Russell TD, Mitra RD, Zhang Q, Wegner DJ, Cole FS, Hamvas A.

BMJ Open Respir Res. 2014;1(1):e000057. doi: 10.1136/bmjresp-2014-000057.

PubMed [citation]

PMID:: 25553246
PMCID:: PMC4265083

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

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV002016364.1

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

Description

In 3 patients from 2 unrelated families (families 5 and 6) with interstitial lung disease-2 (ILD2; 178500), Legendre et al. (2020) identified a heterozygous c.532G-A transition (c.532G-A, NM_001098668.2) in exon 6 of the SFTPA2 gene, resulting in a val178-to-met (V178M) substitution in the CRD domain. The mutation, which was found by direct sequencing, was found at a low frequency in the gnomAD database (3 of 250,974 alleles). One unaffected family member in family 5 carried the mutation, consistent with incomplete penetrance. In vitro functional expression studies in HEK293T cells transfected with the mutation showed normal protein expression with decreased secretion of SFTPA1 compared to controls. Abnormal cytoplasmic retention of mutant SFTPA1 in the alveolar epithelium was considered to contribute to pathogenicity. The proband in family 6 had 2 similarly affected deceased family members, including those with lung cancer, but DNA from those individuals 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

From Alder lab, University of Pittsburgh, SCV002573690.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	research	PubMed (3)

#	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		2	not provided	not provided	not provided

Last Updated: Aug 5, 2023

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