rs17423808

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000372325.7(SFTPA2):c.26C>A(p.Thr9Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 1,350,312 control chromosomes in the GnomAD database, including 280,757 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.52 ( 21170 hom., cov: 27)

Exomes 𝑓: 0.61 ( 259587 hom. )

Consequence

SFTPA2
ENST00000372325.7 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.14

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.684461E-4).

BP6

Variant 10-79559458-G-T is Benign according to our data. Variant chr10-79559458-G-T is described in ClinVar as [Benign]. Clinvar id is 227066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-79559458-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFTPA2	NM_001098668.4 linkuse as main transcript	c.26C>A	p.Thr9Asn	missense_variant	3/6	ENST00000372325.7	NP_001092138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFTPA2	ENST00000372325.7 linkuse as main transcript	c.26C>A	p.Thr9Asn	missense_variant	3/6	1	NM_001098668.4	ENSP00000361400	P1

Frequencies

GnomAD3 genomes

AF:

0.523

AC:

77988

AN:

149154

Hom.:

21171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.390

Gnomad AMI

AF:

0.756

Gnomad AMR

AF:

0.504

Gnomad ASJ

AF:

0.430

Gnomad EAS

AF:

0.533

Gnomad SAS

AF:

0.446

Gnomad FIN

AF:

0.583

Gnomad MID

AF:

0.404

Gnomad NFE

AF:

0.606

Gnomad OTH

AF:

0.494

GnomAD3 exomes

AF:

0.455

AC:

84524

AN:

185672

Hom.:

31716

AF XY:

0.451

AC XY:

44740

AN XY:

99180

show subpopulations

Gnomad AFR exome

AF:

0.259

Gnomad AMR exome

AF:

0.430

Gnomad ASJ exome

AF:

0.334

Gnomad EAS exome

AF:

0.431

Gnomad SAS exome

AF:

0.381

Gnomad FIN exome

AF:

0.529

Gnomad NFE exome

AF:

0.512

Gnomad OTH exome

AF:

0.483

GnomAD4 exome

AF:

0.611

AC:

733932

AN:

1201044

Hom.:

259587

Cov.:

AF XY:

0.604

AC XY:

363151

AN XY:

600936

show subpopulations

Gnomad4 AFR exome

AF:

0.349

Gnomad4 AMR exome

AF:

0.501

Gnomad4 ASJ exome

AF:

0.422

Gnomad4 EAS exome

AF:

0.535

Gnomad4 SAS exome

AF:

0.443

Gnomad4 FIN exome

AF:

0.574

Gnomad4 NFE exome

AF:

0.653

Gnomad4 OTH exome

AF:

0.570

GnomAD4 genome

AF:

0.523

AC:

77999

AN:

149268

Hom.:

21170

Cov.:

AF XY:

0.516

AC XY:

37536

AN XY:

72740

show subpopulations

Gnomad4 AFR

AF:

0.390

Gnomad4 AMR

AF:

0.504

Gnomad4 ASJ

AF:

0.430

Gnomad4 EAS

AF:

0.533

Gnomad4 SAS

AF:

0.445

Gnomad4 FIN

AF:

0.583

Gnomad4 NFE

AF:

0.606

Gnomad4 OTH

AF:

0.490

Alfa

AF:

0.490

Hom.:

3518

Bravo

AF:

0.517

ExAC

AF:

0.358

AC:

43356

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 24950659) -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 12, 2015

p.Thr9Asn in exon 3 of SFTPA2: This variant is not expected to have clinical sig nificance it has been identified in 41% (22324/54314) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP r s1059046). -

SFTPA2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 26, 2021

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

0.14

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.21

DANN

Benign

0.71

Eigen

Benign

-0.87

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.29

.;.;T;T;T

MetaRNN

Benign

0.00037

T;T;T;T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.0

N;N;N;.;.

REVEL

Benign

0.042

Sift

Benign

0.24

T;T;T;.;.

Sift4G

Benign

0.17

T;T;T;.;.

Vest4

0.13

MPC

1.6

ClinPred

0.018

GERP RS

0.64

gMVP

0.28

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