chr10-79557536-G-A

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

2

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

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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
SFTPA2NM_001098668.4 linkc.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 Appris UniProt
SFTPA2ENST00000372325.7 linkc.420C>T p.Ser140Ser synonymous_variant Exon 6 of 6 1 NM_001098668.4 ENSP00000361400.2 Q8IWL1
SFTPA2ENST00000372327.9 linkc.420C>T p.Ser140Ser synonymous_variant Exon 5 of 5 1 ENSP00000361402.5 Q8IWL1
SFTPA2ENST00000417041.1 linkc.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.:
30
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.:
36
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
0
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
0
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.:
30
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
0
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
0
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
DANN
Benign
0.63
PhyloP100
-0.12
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs1965707; hg19: chr10-81317292; COSMIC: COSV64882330; COSMIC: COSV64882330; API