10-79559336-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001320814.1(SFTPA2):c.178G>C(p.Val60Leu) 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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 173 hom., cov: 28)

Exomes 𝑓: 0.023 ( 2528 hom. )

Consequence

SFTPA2
NM_001320814.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.82

Publications

9 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 -20 ACMG points.

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320814.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SFTPA2	NM_001098668.4	MANE Select	c.148G>C	p.Val50Leu	missense	Exon 3 of 6	NP_001092138.1
SFTPA2	NM_001320814.1		c.178G>C	p.Val60Leu	missense	Exon 2 of 5	NP_001307743.1
SFTPA2	NM_001320813.2		c.148G>C	p.Val50Leu	missense	Exon 3 of 6	NP_001307742.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SFTPA2	ENST00000372325.7	TSL:1 MANE Select	c.148G>C	p.Val50Leu	missense	Exon 3 of 6	ENSP00000361400.2
SFTPA2	ENST00000372327.9	TSL:1	c.148G>C	p.Val50Leu	missense	Exon 2 of 5	ENSP00000361402.5
SFTPA2	ENST00000959071.1		c.148G>C	p.Val50Leu	missense	Exon 3 of 6	ENSP00000629130.1

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

GnomAD2 exomes

AF:

0.0247

AC:

5945

AN:

241058

AF XY:

0.0265

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 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

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

African (AFR)

AF:

0.00806

AC:

267

AN:

33122

American (AMR)

AF:

0.0214

AC:

946

AN:

44154

Ashkenazi Jewish (ASJ)

AF:

0.0424

AC:

1073

AN:

25324

East Asian (EAS)

AF:

0.00255

AC:

101

AN:

39666

South Asian (SAS)

AF:

0.0373

AC:

3123

AN:

83770

European-Finnish (FIN)

AF:

0.0247

AC:

1292

AN:

52410

Middle Eastern (MID)

AF:

0.0503

AC:

277

AN:

5506

European-Non Finnish (NFE)

AF:

0.0226

AC:

23471

AN:

1038132

Other (OTH)

AF:

0.0282

AC:

1632

AN:

57966

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.382

Heterozygous variant carriers

1464

2928

4393

5857

7321

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

266

532

798

1064

1330

<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:

0.0412

AC:

6256

AN:

151932

Hom.:

173

Cov.:

AF XY:

0.0399

AC XY:

2963

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.0132

AC:

548

AN:

41510

American (AMR)

AF:

0.0334

AC:

510

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.0558

AC:

193

AN:

3458

East Asian (EAS)

AF:

0.00601

AC:

AN:

5158

South Asian (SAS)

AF:

0.0419

AC:

201

AN:

4802

European-Finnish (FIN)

AF:

0.0340

AC:

360

AN:

10576

Middle Eastern (MID)

AF:

0.0822

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0625

AC:

4243

AN:

67862

Other (OTH)

AF:

0.0480

AC:

101

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

270

540

809

1079

1349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<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:

0.0315

Hom.:

Bravo

AF:

0.0398

ExAC

AF:

0.0400

AC:

4860

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.034

(source)

DANN

Benign

0.71

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.17

MetaRNN

Benign

0.0047

MetaSVM

Benign

-0.94

PhyloP100

-1.8

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.61

REVEL

Benign

0.027

Sift

Benign

0.69

Sift4G

Benign

0.47

Vest4

0.049

MPC

1.6

ClinPred

0.0026

GERP RS

-4.2

PromoterAI

-0.017

Neutral

(source)

gMVP

0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over