chr10-79557536-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001098668.4(SFTPA2):c.420C>T(p.Ser140Ser) 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:5

Conservation

PhyloP100: -0.123

Publications

22 publications found

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 Gene-Disease associations (from GenCC):

interstitial lung disease 2
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
idiopathic pulmonary fibrosis
Inheritance: Unknown, AD Classification: MODERATE, LIMITED Submitted by: Laboratory for Molecular Medicine, Genomics England PanelApp

SFTPA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 227069.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
SFTPA2	NM_001098668.4 link	c.420C>T	p.Ser140Ser	synonymous_variant	Exon 6 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.420C>T	p.Ser140Ser	synonymous_variant	Exon 6 of 6	1	NM_001098668.4	ENSP00000361400.2	Q8IWL1
SFTPA2	ENST00000372327.9 link	c.420C>T	p.Ser140Ser	synonymous_variant	Exon 5 of 5	1		ENSP00000361402.5	Q8IWL1
SFTPA2	ENST00000417041.1 link	c.420C>T	p.Ser140Ser	synonymous_variant	Exon 6 of 6	5		ENSP00000397375.1	X6REF7

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

GnomAD2 exomes

AF:

0.280

AC:

65599

AN:

234178

AF XY:

0.288

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.376

AC:

12296

AN:

32684

American (AMR)

AF:

0.169

AC:

7436

AN:

44118

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

10304

AN:

25768

East Asian (EAS)

AF:

0.447

AC:

17548

AN:

39232

South Asian (SAS)

AF:

0.353

AC:

30078

AN:

85182

European-Finnish (FIN)

AF:

0.290

AC:

15171

AN:

52396

Middle Eastern (MID)

AF:

0.363

AC:

1959

AN:

5396

European-Non Finnish (NFE)

AF:

0.265

AC:

289163

AN:

1091832

Other (OTH)

AF:

0.296

AC:

17618

AN:

59506

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.370

Heterozygous variant carriers

11651

23302

34953

46604

58255

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9628

19256

28884

38512

48140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.308

AC:

46396

AN:

150506

Hom.:

7522

Cov.:

AF XY:

0.309

AC XY:

22696

AN XY:

73494

show subpopulations

African (AFR)

AF:

0.368

AC:

15006

AN:

40820

American (AMR)

AF:

0.222

AC:

3365

AN:

15150

Ashkenazi Jewish (ASJ)

AF:

0.395

AC:

1366

AN:

3458

East Asian (EAS)

AF:

0.467

AC:

2378

AN:

5092

South Asian (SAS)

AF:

0.334

AC:

1576

AN:

4724

European-Finnish (FIN)

AF:

0.273

AC:

2856

AN:

10444

Middle Eastern (MID)

AF:

0.384

AC:

112

AN:

292

European-Non Finnish (NFE)

AF:

0.279

AC:

18868

AN:

67538

Other (OTH)

AF:

0.315

AC:

656

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

1454

2909

4363

5818

7272

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.316

Hom.:

1424

Bravo

AF:

0.307

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 02, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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.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

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

7.2

(source)

DANN

Benign

0.63

PhyloP100

-0.12

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over