10-79559511-C-A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001098668.4(SFTPA2):​c.-23-5G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00259 in 1,585,742 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.012 ( 34 hom., cov: 28)
Exomes 𝑓: 0.0016 ( 27 hom. )

Consequence

SFTPA2
NM_001098668.4 splice_region, intron

Scores

2
Splicing: ADA: 0.00002446
2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.31

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BP6
Variant 10-79559511-C-A is Benign according to our data. Variant chr10-79559511-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3060374.Status of the report is no_assertion_criteria_provided, 0 stars.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0116 (1759/151366) while in subpopulation AFR AF = 0.0381 (1569/41230). AF 95% confidence interval is 0.0365. There are 34 homozygotes in GnomAd4. There are 809 alleles in the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check.
BS2
High AC in GnomAd4 at 1759 AD,Unknown gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SFTPA2NM_001098668.4 linkc.-23-5G>T splice_region_variant, intron_variant Intron 2 of 5 ENST00000372325.7 NP_001092138.1 Q8IWL1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SFTPA2ENST00000372325.7 linkc.-23-5G>T splice_region_variant, intron_variant Intron 2 of 5 1 NM_001098668.4 ENSP00000361400.2 Q8IWL1

Frequencies

GnomAD3 genomes
AF:
0.0116
AC:
1751
AN:
151246
Hom.:
34
Cov.:
28
show subpopulations
Gnomad AFR
AF:
0.0380
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00663
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00236
Gnomad SAS
AF:
0.000209
Gnomad FIN
AF:
0.000286
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000708
Gnomad OTH
AF:
0.0111
GnomAD2 exomes
AF:
0.00363
AC:
719
AN:
198208
AF XY:
0.00275
show subpopulations
Gnomad AFR exome
AF:
0.0392
Gnomad AMR exome
AF:
0.00186
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00253
Gnomad FIN exome
AF:
0.0000600
Gnomad NFE exome
AF:
0.000562
Gnomad OTH exome
AF:
0.00326
GnomAD4 exome
AF:
0.00163
AC:
2341
AN:
1434376
Hom.:
27
Cov.:
55
AF XY:
0.00147
AC XY:
1046
AN XY:
713470
show subpopulations
African (AFR)
AF:
0.0388
AC:
1277
AN:
32942
American (AMR)
AF:
0.00243
AC:
105
AN:
43282
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25848
East Asian (EAS)
AF:
0.00216
AC:
85
AN:
39378
South Asian (SAS)
AF:
0.000586
AC:
50
AN:
85294
European-Finnish (FIN)
AF:
0.000284
AC:
15
AN:
52904
Middle Eastern (MID)
AF:
0.00549
AC:
30
AN:
5466
European-Non Finnish (NFE)
AF:
0.000511
AC:
557
AN:
1089908
Other (OTH)
AF:
0.00374
AC:
222
AN:
59354
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.448
Heterozygous variant carriers
0
67
133
200
266
333
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
52
104
156
208
260
<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:
0.0116
AC:
1759
AN:
151366
Hom.:
34
Cov.:
28
AF XY:
0.0110
AC XY:
809
AN XY:
73874
show subpopulations
African (AFR)
AF:
0.0381
AC:
1569
AN:
41230
American (AMR)
AF:
0.00662
AC:
101
AN:
15256
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3458
East Asian (EAS)
AF:
0.00237
AC:
12
AN:
5072
South Asian (SAS)
AF:
0.000419
AC:
2
AN:
4770
European-Finnish (FIN)
AF:
0.000286
AC:
3
AN:
10498
Middle Eastern (MID)
AF:
0.00340
AC:
1
AN:
294
European-Non Finnish (NFE)
AF:
0.000708
AC:
48
AN:
67784
Other (OTH)
AF:
0.0110
AC:
23
AN:
2096
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.464
Heterozygous variant carriers
0
70
139
209
278
348
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
20
40
60
80
100
<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:
0.000703
Hom.:
3793

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

SFTPA2-related disorder Benign:1
Mar 07, 2019
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

This variant is classified as likely 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
BayesDel_noAF
Benign
-0.97
CADD
Benign
0.19
DANN
Benign
0.49
PhyloP100
-1.3
PromoterAI
-0.073
Neutral
Mutation Taster
=98/2
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000024
dbscSNV1_RF
Benign
0.0040
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

Other links and lift over

dbSNP: rs1650232; hg19: chr10-81319267; API