10-79557536-G-A

Position:

• chr10-79557536-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001098668.4(SFTPA2):​c.420C>T​(p.Ser140Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,586,620 control chromosomes in the GnomAD database, including 68,001 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7522 hom., cov: 30)
  • Exomes 𝑓: 0.28 (60479 hom.)
• Consequence: SFTPA2 NM_001098668.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.123

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 10-79557536-G-A is Benign according to our data. Variant chr10-79557536-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 227069.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-79557536-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.123 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFTPA2	NM_001098668.4	c.420C>T	p.Ser140Ser	synonymous_variant	6/6	ENST00000372325.7	NP_001092138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFTPA2	ENST00000372325.7	c.420C>T	p.Ser140Ser	synonymous_variant	6/6	1	NM_001098668.4	ENSP00000361400.2
SFTPA2	ENST00000372327.9	c.420C>T	p.Ser140Ser	synonymous_variant	5/5	1		ENSP00000361402.5
SFTPA2	ENST00000417041.1	c.420C>T	p.Ser140Ser	synonymous_variant	6/6	5		ENSP00000397375.1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46323 AN: 150386 Hom.: 7500 Cov.: 30

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.313

GnomAD3 exomes AF: 0.280 AC: 65599 AN: 234178 Hom.: 11447 AF XY: 0.288 AC XY: 36496 AN XY: 126786

Gnomad AFR exome AF: 0.348

Gnomad AMR exome AF: 0.154

Gnomad ASJ exome AF: 0.390

Gnomad EAS exome AF: 0.485

Gnomad SAS exome AF: 0.346

Gnomad FIN exome AF: 0.271

Gnomad NFE exome AF: 0.253

Gnomad OTH exome AF: 0.262

GnomAD4 exome AF: 0.280 AC: 401573 AN: 1436114 Hom.: 60479 Cov.: 36 AF XY: 0.283 AC XY: 202058 AN XY: 713970

Gnomad4 AFR exome AF: 0.376

Gnomad4 AMR exome AF: 0.169

Gnomad4 ASJ exome AF: 0.400

Gnomad4 EAS exome AF: 0.447

Gnomad4 SAS exome AF: 0.353

Gnomad4 FIN exome AF: 0.290

Gnomad4 NFE exome AF: 0.265

Gnomad4 OTH exome AF: 0.296

GnomAD4 genome AF: 0.308 AC: 46396 AN: 150506 Hom.: 7522 Cov.: 30 AF XY: 0.309 AC XY: 22696 AN XY: 73494

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.315

Alfa AF: 0.316 Hom.: 1424

Bravo AF: 0.307

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 02, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 12, 2015

p.Ser140Ser in exon 6 of SFTPA2: This variant is not expected to have clinical s ignificance it has been identified in 45% (3704/8134) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs1965707). -

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
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.2
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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

Other links and lift over

dbSNP: rs1965707; hg19: chr10-81317292; COSMIC: COSV64882330; COSMIC: COSV64882330;