10-79555670-T-C

Variant names:

• chr10-79555670-T-C
• rs17881720
• NM_001098668.4:c.*1539A>G

Variant summary

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

The NM_001098668.4(SFTPA2):​c.*1539A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0696 in 152,178 control chromosomes in the GnomAD database, including 534 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 0.070 (534 hom., cov: 32)
• Consequence: SFTPA2 NM_001098668.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.441
• Publications: 2 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 Submitted by: PanelApp Australia, ClinGen
• interstitial lung disease 2

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

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPA2	NM_001098668.4	MANE Select	c.*1539A>G		downstream_gene	N/A	NP_001092138.1	Q8IWL1
	SFTPA2	NM_001320814.1		c.*1539A>G		downstream_gene	N/A	NP_001307743.1
	SFTPA2	NM_001320813.2		c.*1539A>G		downstream_gene	N/A	NP_001307742.1	Q8IWL1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPA2	ENST00000372325.7	TSL:1 MANE Select	c.*1539A>G		downstream_gene	N/A	ENSP00000361400.2	Q8IWL1
	SFTPA2	ENST00000959071.1		c.*1539A>G		downstream_gene	N/A	ENSP00000629130.1
	SFTPA2	ENST00000905087.1		c.*1539A>G		downstream_gene	N/A	ENSP00000575146.1

Frequencies

GnomAD3 genomes AF: 0.0696 AC: 10578 AN: 152060 Hom.: 533 Cov.: 32

Gnomad AFR AF: 0.0296

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0628

Gnomad ASJ AF: 0.0916

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.0705

Gnomad FIN AF: 0.0724

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0766

Gnomad OTH AF: 0.0770

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0696 AC: 10592 AN: 152178 Hom.: 534 Cov.: 32 AF XY: 0.0710 AC XY: 5282 AN XY: 74394

African (AFR) AF: 0.0296 AC: 1230 AN: 41550

American (AMR) AF: 0.0627 AC: 958 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0916 AC: 318 AN: 3470

East Asian (EAS) AF: 0.286 AC: 1477 AN: 5164

South Asian (SAS) AF: 0.0712 AC: 343 AN: 4820

European-Finnish (FIN) AF: 0.0724 AC: 766 AN: 10584

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0766 AC: 5210 AN: 67996

Other (OTH) AF: 0.0804 AC: 170 AN: 2114

Alfa AF: 0.0586 Hom.: 142

Bravo AF: 0.0681

Asia WGS AF: 0.169 AC: 586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.87
PhyloP100		-0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17881720; hg19: chr10-81315426;