10-79557308-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001098668.4(SFTPA2):c.648T>C(p.Pro216=) 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.35

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 -15 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_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.35 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000826 (124/150036) while in subpopulation SAS AF= 0.0136 (64/4718). AF 95% confidence interval is 0.0109. There are 1 homozygotes in gnomad4. There are 72 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 125 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPA2	NM_001098668.4	c.648T>C	p.Pro216=	synonymous_variant	6/6	ENST00000372325.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPA2	ENST00000372325.7	c.648T>C	p.Pro216=	synonymous_variant	6/6	1	NM_001098668.4	P1
SFTPA2	ENST00000372327.9	c.648T>C	p.Pro216=	synonymous_variant	5/5	1		P1

Frequencies

GnomAD3 genomes AF: 0.000834 AC: 125 AN: 149908 Hom.: 1 Cov.: 31

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.: 5 AF XY: 0.000937 AC XY: 127 AN XY: 135542

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.: 15 Cov.: 34 AF XY: 0.00116 AC XY: 842 AN XY: 726314

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.: 1 Cov.: 31 AF XY: 0.000980 AC XY: 72 AN XY: 73460

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.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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). -

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

Other links and lift over

dbSNP: rs17096771; hg19: chr10-81317064; COSMIC: COSV64882209; COSMIC: COSV64882209;