chr10-79559511-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 4P and 16B. PVS1_StrongBP6_Very_StrongBA1

The NM_001320813.2(SFTPA2):c.-26-2G>A variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 1,434,494 control chromosomes in the GnomAD database, including 480,364 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 39999 hom., cov: 28)

Exomes 𝑓: 0.81 ( 440365 hom. )

Consequence

SFTPA2
NM_001320813.2 splice_acceptor, intron

Scores

Splicing: ADA: 0.7087

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 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 4.1, offset of 0 (no position change), new splice context is: gctcacggccatccctccAGcag. 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-T is Benign according to our data. Variant chr10-79559511-C-T is described in ClinVar as [Benign]. Clinvar id is 1247340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-79559511-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPA2	NM_001098668.4 link	c.-23-5G>A		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>A		splice_region_variant, intron_variant	Intron 2 of 5	1	NM_001098668.4	ENSP00000361400.2		Q8IWL1

Frequencies

GnomAD3 genomes

AF:

0.724

AC:

109257

AN:

150818

Hom.:

39988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.631

Gnomad AMI

AF:

0.869

Gnomad AMR

AF:

0.648

Gnomad ASJ

AF:

0.710

Gnomad EAS

AF:

0.739

Gnomad SAS

AF:

0.704

Gnomad FIN

AF:

0.770

Gnomad MID

AF:

0.661

Gnomad NFE

AF:

0.792

Gnomad OTH

AF:

0.702

GnomAD3 exomes

AF:

0.711

AC:

140999

AN:

198208

Hom.:

57812

AF XY:

0.718

AC XY:

76589

AN XY:

106726

show subpopulations

Gnomad AFR exome

AF:

0.598

Gnomad AMR exome

AF:

0.579

Gnomad ASJ exome

AF:

0.711

Gnomad EAS exome

AF:

0.707

Gnomad SAS exome

AF:

0.725

Gnomad FIN exome

AF:

0.770

Gnomad NFE exome

AF:

0.756

Gnomad OTH exome

AF:

0.706

GnomAD4 exome

AF:

0.811

AC:

1040736

AN:

1283558

Hom.:

440365

Cov.:

AF XY:

0.808

AC XY:

518094

AN XY:

640838

show subpopulations

Gnomad4 AFR exome

AF:

0.627

Gnomad4 AMR exome

AF:

0.625

Gnomad4 ASJ exome

AF:

0.722

Gnomad4 EAS exome

AF:

0.765

Gnomad4 SAS exome

AF:

0.740

Gnomad4 FIN exome

AF:

0.766

Gnomad4 NFE exome

AF:

0.839

Gnomad4 OTH exome

AF:

0.775

GnomAD4 genome

AF:

0.724

AC:

109308

AN:

150936

Hom.:

39999

Cov.:

AF XY:

0.719

AC XY:

52971

AN XY:

73652

show subpopulations

Gnomad4 AFR

AF:

0.630

Gnomad4 AMR

AF:

0.647

Gnomad4 ASJ

AF:

0.710

Gnomad4 EAS

AF:

0.738

Gnomad4 SAS

AF:

0.705

Gnomad4 FIN

AF:

0.770

Gnomad4 NFE

AF:

0.792

Gnomad4 OTH

AF:

0.697

Alfa

AF:

0.690

Hom.:

3793

Bravo

AF:

0.719

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 23328842, 9003399) -

Interstitial lung disease 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

SFTPA2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 01, 2021

This variant is classified as 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

-0.92

CADD

Benign

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.71

dbscSNV1_RF

Benign

0.55

SpliceAI score (max)

0.63

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.63

Position offset: -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