rs1965707

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001098668.4(SFTPA2):c.420C>T(p.Ser140=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,586,620 control chromosomes in the GnomAD database, including 68,001 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7522 hom., cov: 30)

Exomes 𝑓: 0.28 ( 60479 hom. )

Consequence

SFTPA2
NM_001098668.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.123

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 10-79557536-G-A is Benign according to our data. Variant chr10-79557536-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 227069.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-79557536-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.123 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPA2	NM_001098668.4 linkuse as main transcript	c.420C>T	p.Ser140=	synonymous_variant	6/6	ENST00000372325.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SFTPA2	ENST00000372325.7 linkuse as main transcript	c.420C>T	p.Ser140=	synonymous_variant	6/6	1	NM_001098668.4	P1
SFTPA2	ENST00000372327.9 linkuse as main transcript	c.420C>T	p.Ser140=	synonymous_variant	5/5	1		P1
SFTPA2	ENST00000417041.1 linkuse as main transcript	c.420C>T	p.Ser140=	synonymous_variant	6/6	5

Frequencies

GnomAD3 genomes

AF:

0.308

AC:

46323

AN:

150386

Hom.:

7500

Cov.:

show subpopulations

Gnomad AFR

AF:

0.367

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.395

Gnomad EAS

AF:

0.467

Gnomad SAS

AF:

0.331

Gnomad FIN

AF:

0.273

Gnomad MID

AF:

0.385

Gnomad NFE

AF:

0.279

Gnomad OTH

AF:

0.313

GnomAD3 exomes

AF:

0.280

AC:

65599

AN:

234178

Hom.:

11447

AF XY:

0.288

AC XY:

36496

AN XY:

126786

show subpopulations

Gnomad AFR exome

AF:

0.348

Gnomad AMR exome

AF:

0.154

Gnomad ASJ exome

AF:

0.390

Gnomad EAS exome

AF:

0.485

Gnomad SAS exome

AF:

0.346

Gnomad FIN exome

AF:

0.271

Gnomad NFE exome

AF:

0.253

Gnomad OTH exome

AF:

0.262

GnomAD4 exome

AF:

0.280

AC:

401573

AN:

1436114

Hom.:

60479

Cov.:

AF XY:

0.283

AC XY:

202058

AN XY:

713970

show subpopulations

Gnomad4 AFR exome

AF:

0.376

Gnomad4 AMR exome

AF:

0.169

Gnomad4 ASJ exome

AF:

0.400

Gnomad4 EAS exome

AF:

0.447

Gnomad4 SAS exome

AF:

0.353

Gnomad4 FIN exome

AF:

0.290

Gnomad4 NFE exome

AF:

0.265

Gnomad4 OTH exome

AF:

0.296

GnomAD4 genome

AF:

0.308

AC:

46396

AN:

150506

Hom.:

7522

Cov.:

AF XY:

0.309

AC XY:

22696

AN XY:

73494

show subpopulations

Gnomad4 AFR

AF:

0.368

Gnomad4 AMR

AF:

0.222

Gnomad4 ASJ

AF:

0.395

Gnomad4 EAS

AF:

0.467

Gnomad4 SAS

AF:

0.334

Gnomad4 FIN

AF:

0.273

Gnomad4 NFE

AF:

0.279

Gnomad4 OTH

AF:

0.315

Alfa

AF:

0.316

Hom.:

1424

Bravo

AF:

0.307

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Aug 02, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 12, 2015

p.Ser140Ser in exon 6 of SFTPA2: This variant is not expected to have clinical s ignificance it has been identified in 45% (3704/8134) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs1965707). -

Interstitial lung disease 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

Cadd

Benign

7.2

Dann

Benign

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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