Variant 10-79557308-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001098668.4(SFTPA2):c.648T>C(p.Pro216Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000919 in 1,610,236 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00083 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00093 ( 15 hom. )

Consequence

SFTPA2
NM_001098668.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.35

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 10-79557308-A-G is Benign according to our data. Variant chr10-79557308-A-G is described in ClinVar as [Benign]. Clinvar id is 227070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.35 with no splicing effect.

BS2

High AC in GnomAd4 at 124 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFTPA2	NM_001098668.4 link	c.648T>C	p.Pro216Pro	synonymous_variant	6/6	ENST00000372325.7	NP_001092138.1	Q8IWL1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFTPA2	ENST00000372325.7 link	c.648T>C	p.Pro216Pro	synonymous_variant	6/6	1	NM_001098668.4	ENSP00000361400.2		Q8IWL1
SFTPA2	ENST00000372327.9 link	c.648T>C	p.Pro216Pro	synonymous_variant	5/5	1		ENSP00000361402.5		Q8IWL1

Frequencies

GnomAD3 genomes

AF:

0.000834

AC:

125

AN:

149908

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000596

Gnomad ASJ

AF:

0.000294

Gnomad EAS

AF:

0.000786

Gnomad SAS

AF:

0.0138

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000537

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000797

AC:

200

AN:

250946

Hom.:

AF XY:

0.000937

AC XY:

127

AN XY:

135542

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.00519

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000158

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000929

AC:

1356

AN:

1460200

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

842

AN XY:

726314

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000515

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.00974

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000365

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.000826

AC:

124

AN:

150036

Hom.:

Cov.:

AF XY:

0.000980

AC XY:

AN XY:

73460

show subpopulations

Gnomad4 AFR

AF:

0.000244

Gnomad4 AMR

AF:

0.000596

Gnomad4 ASJ

AF:

0.000294

Gnomad4 EAS

AF:

0.000787

Gnomad4 SAS

AF:

0.0136

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000537

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000718

Hom.:

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

Dec 10, 2015

p.Pro216Pro in exon 6 of SFTPA2: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 0.9% (145/16444) of South Asian chromosomes, including 4 homozygotes, by the Exome Aggregation Co nsortium (ExAC, http://exac.broadinstitute.org;dbSNP rs17096771). -

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

-0.92

CADD

Benign

1.3

DANN

Benign

0.55

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