rs17886395

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.271G>C(p.Ala91Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,613,720 control chromosomes in the GnomAD database, including 21,037 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 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 0.17 ( 2363 hom., cov: 32)

Exomes 𝑓: 0.15 ( 18674 hom. )

Consequence

SFTPA2
NM_001098668.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0340

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=0.018847167).

BP6

Variant 10-79558907-C-G is Benign according to our data. Variant chr10-79558907-C-G is described in ClinVar as [Benign]. Clinvar id is 227067.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPA2	NM_001098668.4 link	c.271G>C	p.Ala91Pro	missense_variant	Exon 4 of 6	ENST00000372325.7	NP_001092138.1	Q8IWL1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SFTPA2	ENST00000372325.7 link	c.271G>C	p.Ala91Pro	missense_variant	Exon 4 of 6	1	NM_001098668.4	ENSP00000361400.2	Q8IWL1
SFTPA2	ENST00000372327.9 link	c.271G>C	p.Ala91Pro	missense_variant	Exon 3 of 5	1		ENSP00000361402.5	Q8IWL1
SFTPA2	ENST00000417041.1 link	c.271G>C	p.Ala91Pro	missense_variant	Exon 4 of 6	5		ENSP00000397375.1	X6REF7
SFTPA2	ENST00000492049.1 link	c.271G>C	p.Ala91Pro	missense_variant	Exon 2 of 2	5		ENSP00000473275.1	R4GMN3

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25407

AN:

151868

Hom.:

2350

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.0713

Gnomad AMR

AF:

0.243

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.281

Gnomad SAS

AF:

0.271

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.169

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.183

GnomAD3 exomes

AF:

0.189

AC:

47412

AN:

251402

Hom.:

5077

AF XY:

0.188

AC XY:

25500

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.168

Gnomad AMR exome

AF:

0.283

Gnomad ASJ exome

AF:

0.147

Gnomad EAS exome

AF:

0.295

Gnomad SAS exome

AF:

0.251

Gnomad FIN exome

AF:

0.136

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.178

GnomAD4 exome

AF:

0.153

AC:

223882

AN:

1461732

Hom.:

18674

Cov.:

AF XY:

0.156

AC XY:

113246

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.164

Gnomad4 AMR exome

AF:

0.278

Gnomad4 ASJ exome

AF:

0.148

Gnomad4 EAS exome

AF:

0.257

Gnomad4 SAS exome

AF:

0.252

Gnomad4 FIN exome

AF:

0.138

Gnomad4 NFE exome

AF:

0.136

Gnomad4 OTH exome

AF:

0.166

GnomAD4 genome

AF:

0.168

AC:

25474

AN:

151988

Hom.:

2363

Cov.:

AF XY:

0.172

AC XY:

12745

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.169

Gnomad4 AMR

AF:

0.244

Gnomad4 ASJ

AF:

0.149

Gnomad4 EAS

AF:

0.282

Gnomad4 SAS

AF:

0.271

Gnomad4 FIN

AF:

0.124

Gnomad4 NFE

AF:

0.142

Gnomad4 OTH

AF:

0.190

Alfa

AF:

0.151

Hom.:

586

Bravo

AF:

0.174

TwinsUK

AF:

0.128

AC:

474

ALSPAC

AF:

0.134

AC:

517

ESP6500AA

AF:

0.162

AC:

713

ESP6500EA

AF:

0.143

AC:

1226

ExAC

AF:

0.186

AC:

22544

Asia WGS

AF:

0.302

AC:

1047

AN:

3478

EpiCase

AF:

0.145

EpiControl

AF:

0.144

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 16292672, 20466729) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Nov 26, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Ala91Pro in exon 4 of SFTPA2: This variant is not expected to have clinical si gnificance because it has been identified in 14.3% (1226/8592) of European Ameri can chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington. edu/EVS/; dbSNP rs17886395). -

SFTPA2-related disorder

Benign:1

Apr 29, 2021

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.27

CADD

Benign

6.0

DANN

Benign

0.066

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00015

LIST_S2

Benign

0.36

.;.;T;T

MetaRNN

Benign

0.019

T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.47

PROVEAN

Benign

2.7

N;N;N;.

REVEL

Benign

0.17

Sift

Benign

1.0

T;T;T;.

Sift4G

Benign

1.0

T;T;T;.

Vest4

0.13

MPC

0.0036

ClinPred

0.00058

GERP RS

1.6

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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