Variant rs182465294 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000372325.7(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
ENST00000372325.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.633

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 -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1499 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFTPA2	NM_001098668.4 linkuse as main transcript	c.292+11C>T		intron_variant		ENST00000372325.7	NP_001092138.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
SFTPA2	ENST00000372325.7 linkuse as main transcript	c.292+11C>T	intron_variant	1	NM_001098668.4	ENSP00000361400	P1
SFTPA2	ENST00000372327.9 linkuse as main transcript	c.292+11C>T	intron_variant	1		ENSP00000361402	P1
SFTPA2	ENST00000417041.1 linkuse as main transcript	c.292+11C>T	intron_variant	5		ENSP00000397375
SFTPA2	ENST00000492049.1 linkuse as main transcript		downstream_gene_variant	5		ENSP00000473275

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

GnomAD3 exomes

AF:

0.00557

AC:

1401

AN:

251330

Hom.:

AF XY:

0.00549

AC XY:

746

AN XY:

135846

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 SAS exome

AF:

0.00712

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

Gnomad4 AFR exome

AF:

0.0238

Gnomad4 AMR exome

AF:

0.00461

Gnomad4 ASJ exome

AF:

0.00742

Gnomad4 EAS exome

AF:

0.00290

Gnomad4 SAS exome

AF:

0.00711

Gnomad4 FIN exome

AF:

0.000599

Gnomad4 NFE exome

AF:

0.00311

Gnomad4 OTH exome

AF:

0.00623

GnomAD4 genome

AF:

0.00986

AC:

1499

AN:

152050

Hom.:

Cov.:

AF XY:

0.00962

AC XY:

715

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0252

Gnomad4 AMR

AF:

0.00622

Gnomad4 ASJ

AF:

0.00837

Gnomad4 EAS

AF:

0.00329

Gnomad4 SAS

AF:

0.00624

Gnomad4 FIN

AF:

0.0000945

Gnomad4 NFE

AF:

0.00368

Gnomad4 OTH

AF:

0.0128

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

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 16, 2016

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.92

DANN

Benign

0.92

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

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