rs1650232

chr10-79559511-C-Achr10-79559511-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001098668.4(SFTPA2):c.-23-5G>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00259 in 1,585,742 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (34 hom., cov: 28)
  • Exomes 𝑓: 0.0016 (27 hom.)
• Consequence: SFTPA2 NM_001098668.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002446
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.31

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 10-79559511-C-A is Benign according to our data. Variant chr10-79559511-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3060374.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0116 (1759/151366) while in subpopulation AFR AF= 0.0381 (1569/41230). AF 95% confidence interval is 0.0365. There are 34 homozygotes in gnomad4. There are 809 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 1751 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPA2	NM_001098668.4	c.-23-5G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000372325.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPA2	ENST00000372325.7	c.-23-5G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001098668.4	P1

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1751 AN: 151246 Hom.: 34 Cov.: 28

Gnomad AFR AF: 0.0380

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00663

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00236

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.000286

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000708

Gnomad OTH AF: 0.0111

GnomAD3 exomes AF: 0.00363 AC: 719 AN: 198208 Hom.: 21 AF XY: 0.00275 AC XY: 294 AN XY: 106726

Gnomad AFR exome AF: 0.0392

Gnomad AMR exome AF: 0.00186

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00253

Gnomad SAS exome AF: 0.000687

Gnomad FIN exome AF: 0.0000600

Gnomad NFE exome AF: 0.000562

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00163 AC: 2341 AN: 1434376 Hom.: 27 Cov.: 55 AF XY: 0.00147 AC XY: 1046 AN XY: 713470

Gnomad4 AFR exome AF: 0.0388

Gnomad4 AMR exome AF: 0.00243

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00216

Gnomad4 SAS exome AF: 0.000586

Gnomad4 FIN exome AF: 0.000284

Gnomad4 NFE exome AF: 0.000511

Gnomad4 OTH exome AF: 0.00374

GnomAD4 genome AF: 0.0116 AC: 1759 AN: 151366 Hom.: 34 Cov.: 28 AF XY: 0.0110 AC XY: 809 AN XY: 73874

Gnomad4 AFR AF: 0.0381

Gnomad4 AMR AF: 0.00662

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00237

Gnomad4 SAS AF: 0.000419

Gnomad4 FIN AF: 0.000286

Gnomad4 NFE AF: 0.000708

Gnomad4 OTH AF: 0.0110

Alfa AF: 0.000703 Hom.: 3793

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SFTPA2-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 07, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.19
Dann	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000024
dbscSNV1_RF	Benign	0.0040
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: rs1650232; hg19: chr10-81319267;