10-79559457-GGT-AGA

Variant names:

• chr10-79559457-GGT-AGA
• NM_001098668.4:c.25_27delACCinsTCT
• SFTPA2 p.Thr9Ser

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001098668.4(SFTPA2):​c.25_27delACCinsTCT​(p.Thr9Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T9N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 27)
• Consequence: SFTPA2 NM_001098668.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.682
• Publications: 0 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: ClinGen, PanelApp Australia
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.25_27delACCinsTCT	p.Thr9Ser	missense	N/A	NP_001092138.1	Q8IWL1
	SFTPA2	NM_001320814.1		c.55_57delACCinsTCT	p.Thr19Ser	missense	N/A	NP_001307743.1
	SFTPA2	NM_001320813.2		c.25_27delACCinsTCT	p.Thr9Ser	missense	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.25_27delACCinsTCT	p.Thr9Ser	missense	N/A	ENSP00000361400.2	Q8IWL1
	SFTPA2	ENST00000372327.9	TSL:1	c.25_27delACCinsTCT	p.Thr9Ser	missense	N/A	ENSP00000361402.5	Q8IWL1
	SFTPA2	ENST00000640627.1	TSL:1	c.70_72delACCinsTCT	p.Thr24Ser	missense	N/A	ENSP00000492537.1	A0A1W2PR89

Frequencies

GnomAD3 genomes Cov.: 27

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

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.68

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-81319213;