rs182465294

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001098668.4(SFTPA2):c.292+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00456 in 1,613,858 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0099 ( 12 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 32 hom. )

Consequence

SFTPA2
NM_001098668.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.633

Publications

1 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 (BayesDel_noAF=-0.74).

BP6

Variant 10-79558875-G-A is Benign according to our data. Variant chr10-79558875-G-A is described in ClinVar as Benign. ClinVar VariationId is 227068.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00986 (1499/152050) while in subpopulation AFR AF = 0.0252 (1046/41454). AF 95% confidence interval is 0.024. There are 12 homozygotes in GnomAd4. There are 715 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1499 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPA2	NM_001098668.4 link	c.292+11C>T		intron_variant	Intron 4 of 5	ENST00000372325.7	NP_001092138.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
SFTPA2	ENST00000372325.7 link	c.292+11C>T	intron_variant	Intron 4 of 5	1	NM_001098668.4	ENSP00000361400.2
SFTPA2	ENST00000372327.9 link	c.292+11C>T	intron_variant	Intron 3 of 4	1		ENSP00000361402.5
SFTPA2	ENST00000417041.1 link	c.292+11C>T	intron_variant	Intron 4 of 5	5		ENSP00000397375.1
SFTPA2	ENST00000492049.1 link	c.*10C>T	downstream_gene_variant		5		ENSP00000473275.1

Frequencies

GnomAD3 genomes

AF:

0.00979

AC:

1488

AN:

151932

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0250

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00629

Gnomad ASJ

AF:

0.00837

Gnomad EAS

AF:

0.00328

Gnomad SAS

AF:

0.00644

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00368

Gnomad OTH

AF:

0.0125

GnomAD2 exomes

AF:

0.00557

AC:

1401

AN:

251330

AF XY:

0.00549

show subpopulations

Gnomad AFR exome

AF:

0.0254

Gnomad AMR exome

AF:

0.00399

Gnomad ASJ exome

AF:

0.00685

Gnomad EAS exome

AF:

0.00375

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00407

Gnomad OTH exome

AF:

0.00440

GnomAD4 exome

AF:

0.00401

AC:

5860

AN:

1461808

Hom.:

Cov.:

AF XY:

0.00419

AC XY:

3050

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.0238

AC:

796

AN:

33470

American (AMR)

AF:

0.00461

AC:

206

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00742

AC:

194

AN:

26136

East Asian (EAS)

AF:

0.00290

AC:

115

AN:

39698

South Asian (SAS)

AF:

0.00711

AC:

613

AN:

86256

European-Finnish (FIN)

AF:

0.000599

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.0123

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00311

AC:

3457

AN:

1111964

Other (OTH)

AF:

0.00623

AC:

376

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

347

693

1040

1386

1733

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

272

408

544

680

<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:

0.00986

AC:

1499

AN:

152050

Hom.:

Cov.:

AF XY:

0.00962

AC XY:

715

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0252

AC:

1046

AN:

41454

American (AMR)

AF:

0.00622

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00837

AC:

AN:

3464

East Asian (EAS)

AF:

0.00329

AC:

AN:

5172

South Asian (SAS)

AF:

0.00624

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.0000945

AC:

AN:

10578

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00368

AC:

250

AN:

67974

Other (OTH)

AF:

0.0128

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

159

239

318

398

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

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:

0.00407

Hom.:

Bravo

AF:

0.0107

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 16, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

c.292+11C>T in intron 4 of SFTPA2: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence. I t has been identified in 2.7% (278/10396) of African chromosomes including 2 hom ozygotes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs182465294). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.92

(source)

DANN

Benign

0.92

PhyloP100

-0.63

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over