rs17879335

Variant names:

• chr10-79556699-C-A
• rs17879335
• NM_001098668.4:c.*510G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098668.4(SFTPA2):​c.*510G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 150,714 control chromosomes in the GnomAD database, including 10,750 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.39 (10750 hom., cov: 33)
  • Exomes 𝑓: 0.33 (2237 hom.)
  • Failed GnomAD Quality Control
• Consequence: SFTPA2 NM_001098668.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• interstitial lung disease 2

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• idiopathic pulmonary fibrosis

  Inheritance: Unknown, AD Classification: MODERATE, LIMITED Submitted by: Laboratory for Molecular Medicine, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098668.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPA2	NM_001098668.4	MANE Select	c.*510G>T		3_prime_UTR	Exon 6 of 6	NP_001092138.1
	SFTPA2	NM_001320814.1		c.*510G>T		3_prime_UTR	Exon 5 of 5	NP_001307743.1
	SFTPA2	NM_001320813.2		c.*510G>T		3_prime_UTR	Exon 6 of 6	NP_001307742.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPA2	ENST00000372325.7	TSL:1 MANE Select	c.*510G>T		3_prime_UTR	Exon 6 of 6	ENSP00000361400.2

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58170 AN: 150598 Hom.: 10700 Cov.: 33

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.403

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.334 AC: 11732 AN: 35100 Hom.: 2237 Cov.: 0 AF XY: 0.347 AC XY: 6174 AN XY: 17768

African (AFR) AF: 0.384 AC: 331 AN: 862

American (AMR) AF: 0.393 AC: 1324 AN: 3366

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 246 AN: 640

East Asian (EAS) AF: 0.455 AC: 945 AN: 2076

South Asian (SAS) AF: 0.498 AC: 1748 AN: 3508

European-Finnish (FIN) AF: 0.291 AC: 326 AN: 1122

Middle Eastern (MID) AF: 0.371 AC: 43 AN: 116

European-Non Finnish (NFE) AF: 0.288 AC: 6202 AN: 21572

Other (OTH) AF: 0.308 AC: 567 AN: 1838

GnomAD4 genome AF: 0.387 AC: 58286 AN: 150714 Hom.: 10750 Cov.: 33 AF XY: 0.391 AC XY: 28775 AN XY: 73676

African (AFR) AF: 0.436 AC: 17729 AN: 40656

American (AMR) AF: 0.397 AC: 6026 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1625 AN: 3454

East Asian (EAS) AF: 0.483 AC: 2486 AN: 5142

South Asian (SAS) AF: 0.535 AC: 2552 AN: 4774

European-Finnish (FIN) AF: 0.318 AC: 3350 AN: 10534

Middle Eastern (MID) AF: 0.448 AC: 130 AN: 290

European-Non Finnish (NFE) AF: 0.344 AC: 23320 AN: 67696

Other (OTH) AF: 0.409 AC: 854 AN: 2088

Alfa AF: 0.396 Hom.: 1315

Bravo AF: 0.401

Asia WGS AF: 0.527 AC: 1833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.52
DANN	Benign	0.20
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17879335; hg19: chr10-81316455;