10-79557289-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The NM_001098668.4(SFTPA2):c.667C>A(p.Gln223Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,613,734 control chromosomes in the GnomAD database, including 38,163 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5277 hom., cov: 32)

Exomes 𝑓: 0.21 ( 32886 hom. )

Consequence

SFTPA2
NM_001098668.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.945

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 Benign. Variant got -18 ACMG points.

PM1

In a disulfide_bond (size 91) in uniprot entity SFPA2_HUMAN there are 11 pathogenic changes around while only 0 benign (100%) in NM_001098668.4

BP4

Computational evidence support a benign effect (MetaRNN=0.0025300682).

BP6

Variant 10-79557289-G-T is Benign according to our data. Variant chr10-79557289-G-T is described in ClinVar as [Benign]. Clinvar id is 227071.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-79557289-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPA2	NM_001098668.4 link	c.667C>A	p.Gln223Lys	missense_variant	Exon 6 of 6	ENST00000372325.7	NP_001092138.1	Q8IWL1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPA2	ENST00000372325.7 link	c.667C>A	p.Gln223Lys	missense_variant	Exon 6 of 6	1	NM_001098668.4	ENSP00000361400.2		Q8IWL1
SFTPA2	ENST00000372327.9 link	c.667C>A	p.Gln223Lys	missense_variant	Exon 5 of 5	1		ENSP00000361402.5		Q8IWL1

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

37959

AN:

151766

Hom.:

5265

Cov.:

show subpopulations

Gnomad AFR

AF:

0.370

Gnomad AMI

AF:

0.135

Gnomad AMR

AF:

0.165

Gnomad ASJ

AF:

0.305

Gnomad EAS

AF:

0.189

Gnomad SAS

AF:

0.268

Gnomad FIN

AF:

0.206

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.205

Gnomad OTH

AF:

0.245

GnomAD3 exomes

AF:

0.217

AC:

54596

AN:

251408

Hom.:

6547

AF XY:

0.223

AC XY:

30291

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.373

Gnomad AMR exome

AF:

0.131

Gnomad ASJ exome

AF:

0.307

Gnomad EAS exome

AF:

0.192

Gnomad SAS exome

AF:

0.286

Gnomad FIN exome

AF:

0.212

Gnomad NFE exome

AF:

0.201

Gnomad OTH exome

AF:

0.202

GnomAD4 exome

AF:

0.207

AC:

301937

AN:

1461850

Hom.:

32886

Cov.:

AF XY:

0.210

AC XY:

152941

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.385

Gnomad4 AMR exome

AF:

0.137

Gnomad4 ASJ exome

AF:

0.309

Gnomad4 EAS exome

AF:

0.196

Gnomad4 SAS exome

AF:

0.289

Gnomad4 FIN exome

AF:

0.215

Gnomad4 NFE exome

AF:

0.194

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.250

AC:

38017

AN:

151884

Hom.:

5277

Cov.:

AF XY:

0.249

AC XY:

18518

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.370

Gnomad4 AMR

AF:

0.165

Gnomad4 ASJ

AF:

0.305

Gnomad4 EAS

AF:

0.188

Gnomad4 SAS

AF:

0.269

Gnomad4 FIN

AF:

0.206

Gnomad4 NFE

AF:

0.205

Gnomad4 OTH

AF:

0.244

Alfa

AF:

0.228

Hom.:

1549

Bravo

AF:

0.248

TwinsUK

AF:

0.190

AC:

705

ALSPAC

AF:

0.188

AC:

724

ESP6500AA

AF:

0.358

AC:

1576

ESP6500EA

AF:

0.200

AC:

1718

ExAC

AF:

0.222

AC:

26906

EpiCase

AF:

0.215

EpiControl

AF:

0.212

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	May 06, 2020	This variant is associated with the following publications: (PMID: 26436397, 24950659, 16292672, 23056344, 20466729) -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Nov 26, 2014

p.Gln223Lys in exon 6 of SFTPA2: This variant is not expected to have clinical s ignificance because it has been identified in 36% (1576/4406) of African America n chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.ed u/EVS/; dbSNP rs1965708). -

Interstitial lung disease 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.88

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.20

DANN

Benign

0.30

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0024

MetaRNN

Benign

0.0025

T;T

MetaSVM

Benign

-0.90

PrimateAI

Benign

0.37

PROVEAN

Benign

0.13

N;N

REVEL

Benign

0.014

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Vest4

0.047

MPC

1.3

ClinPred

0.0031

GERP RS

-3.2

gMVP

0.50

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