rs192907309

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The NM_001098668.4(SFTPA2):c.148G>C(p.Val50Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 1,531,982 control chromosomes in the GnomAD database, including 2,701 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.041 ( 173 hom., cov: 28)

Exomes 𝑓: 0.023 ( 2528 hom. )

Consequence

SFTPA2
NM_001098668.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.82

Variant links:

Genes affected

SFTPA2 (HGNC:10799): (surfactant protein A2) This gene is one of several genes encoding pulmonary-surfactant associated proteins (SFTPA) located on chromosome 10. Mutations in this gene and a highly similar gene located nearby, which affect the highly conserved carbohydrate recognition domain, are associated with idiopathic pulmonary fibrosis. The current version of the assembly displays only a single centromeric SFTPA gene pair rather than the two gene pairs shown in the previous assembly which were thought to have resulted from a duplication. [provided by RefSeq, Sep 2009]

SFTPA2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

PM1

In a chain Pulmonary surfactant-associated protein A2 (size 227) in uniprot entity SFPA2_HUMAN there are 11 pathogenic changes around while only 3 benign (79%) in NM_001098668.4

BP4

Computational evidence support a benign effect (MetaRNN=0.0046575665).

BP6

Variant 10-79559336-C-G is Benign according to our data. Variant chr10-79559336-C-G is described in ClinVar as [Benign]. Clinvar id is 227065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.061 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPA2	NM_001098668.4 link	c.148G>C	p.Val50Leu	missense_variant	Exon 3 of 6	ENST00000372325.7	NP_001092138.1	Q8IWL1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPA2	ENST00000372325.7 link	c.148G>C	p.Val50Leu	missense_variant	Exon 3 of 6	1	NM_001098668.4	ENSP00000361400.2		Q8IWL1

Frequencies

GnomAD3 genomes

AF:

0.0412

AC:

6255

AN:

151814

Hom.:

172

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0132

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.0335

Gnomad ASJ

AF:

0.0558

Gnomad EAS

AF:

0.00580

Gnomad SAS

AF:

0.0416

Gnomad FIN

AF:

0.0340

Gnomad MID

AF:

0.0828

Gnomad NFE

AF:

0.0625

Gnomad OTH

AF:

0.0490

GnomAD3 exomes

AF:

0.0247

AC:

5945

AN:

241058

Hom.:

300

AF XY:

0.0265

AC XY:

3436

AN XY:

129744

show subpopulations

Gnomad AFR exome

AF:

0.00751

Gnomad AMR exome

AF:

0.0176

Gnomad ASJ exome

AF:

0.0413

Gnomad EAS exome

AF:

0.00267

Gnomad SAS exome

AF:

0.0305

Gnomad FIN exome

AF:

0.0119

Gnomad NFE exome

AF:

0.0323

Gnomad OTH exome

AF:

0.0305

GnomAD4 exome

AF:

0.0233

AC:

32182

AN:

1380050

Hom.:

2528

Cov.:

AF XY:

0.0247

AC XY:

16998

AN XY:

687524

show subpopulations

Gnomad4 AFR exome

AF:

0.00806

Gnomad4 AMR exome

AF:

0.0214

Gnomad4 ASJ exome

AF:

0.0424

Gnomad4 EAS exome

AF:

0.00255

Gnomad4 SAS exome

AF:

0.0373

Gnomad4 FIN exome

AF:

0.0247

Gnomad4 NFE exome

AF:

0.0226

Gnomad4 OTH exome

AF:

0.0282

GnomAD4 genome

AF:

0.0412

AC:

6256

AN:

151932

Hom.:

173

Cov.:

AF XY:

0.0399

AC XY:

2963

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.0132

Gnomad4 AMR

AF:

0.0334

Gnomad4 ASJ

AF:

0.0558

Gnomad4 EAS

AF:

0.00601

Gnomad4 SAS

AF:

0.0419

Gnomad4 FIN

AF:

0.0340

Gnomad4 NFE

AF:

0.0625

Gnomad4 OTH

AF:

0.0480

Alfa

AF:

0.0315

Hom.:

Bravo

AF:

0.0398

ExAC

AF:

0.0400

AC:

4860

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 12, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Val50Leu in exon 3 of SFTPA2: This variant is not expected to have clinical si gnificance it has been identified in 5% (3378/62636) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs 192907309). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.034

DANN

Benign

0.71

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.17

.;.;T;T

MetaRNN

Benign

0.0047

T;T;T;T

MetaSVM

Benign

-0.94

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.61

N;N;N;.

REVEL

Benign

0.027

Sift

Benign

0.69

T;T;T;.

Sift4G

Benign

0.47

T;T;T;.

Vest4

0.049

MPC

1.6

ClinPred

0.0026

GERP RS

-4.2

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over