Variant rs1650232 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 4P and 9B. PVS1_StrongBP6BS1BS2

The NM_001320813.2(SFTPA2):c.-26-2G>T variant causes a splice acceptor, 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_001320813.2 splice_acceptor, intron

Scores

Splicing: ADA: 0.00002446

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.31

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.26506025 fraction of the gene. Cryptic splice site detected, with MaxEntScore 10, offset of 3, new splice context is: cacggccatccctcctgcAGgag. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.

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 male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1759 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPA2	NM_001098668.4 link	c.-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
SFTPA2	ENST00000372325.7 link	c.-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.:

Cov.:

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

GnomAD3 exomes

AF:

0.00363

AC:

719

AN:

198208

Hom.:

AF XY:

0.00275

AC XY:

294

AN XY:

106726

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 SAS exome

AF:

0.000687

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.:

Cov.:

AF XY:

0.00147

AC XY:

1046

AN XY:

713470

show subpopulations

Gnomad4 AFR exome

AF:

0.0388

Gnomad4 AMR exome

AF:

0.00243

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00216

Gnomad4 SAS exome

AF:

0.000586

Gnomad4 FIN exome

AF:

0.000284

Gnomad4 NFE exome

AF:

0.000511

Gnomad4 OTH exome

AF:

0.00374

GnomAD4 genome

AF:

0.0116

AC:

1759

AN:

151366

Hom.:

Cov.:

AF XY:

0.0110

AC XY:

809

AN XY:

73874

show subpopulations

Gnomad4 AFR

AF:

0.0381

Gnomad4 AMR

AF:

0.00662

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00237

Gnomad4 SAS

AF:

0.000419

Gnomad4 FIN

AF:

0.000286

Gnomad4 NFE

AF:

0.000708

Gnomad4 OTH

AF:

0.0110

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

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

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