SFTPA2 p.Thr9Ser

Variant names:

• chr10-79559459-T-A
• NM_001098668.4:c.25A>T
• SFTPA2 p.Thr9Ser

Your query was ambiguous. Multiple possible variants found:

• chr10-79559459-T-A
• chr10-79559458-G-C
• chr10-79559457-GGT-AGA
• chr10-79559457-GGT-TGA
• chr10-79559457-GGT-CGA
• chr10-79559457-GG-AC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001098668.4(SFTPA2):​c.25A>T​(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. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. 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: 28)
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1332455).

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.25A>T	p.Thr9Ser	missense	Exon 3 of 6	NP_001092138.1	Q8IWL1
	SFTPA2	NM_001320814.1		c.55A>T	p.Thr19Ser	missense	Exon 2 of 5	NP_001307743.1
	SFTPA2	NM_001320813.2		c.25A>T	p.Thr9Ser	missense	Exon 3 of 6	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.25A>T	p.Thr9Ser	missense	Exon 3 of 6	ENSP00000361400.2	Q8IWL1
	SFTPA2	ENST00000372327.9	TSL:1	c.25A>T	p.Thr9Ser	missense	Exon 2 of 5	ENSP00000361402.5	Q8IWL1
	SFTPA2	ENST00000640627.1	TSL:1	c.70A>T	p.Thr24Ser	missense	Exon 3 of 3	ENSP00000492537.1	A0A1W2PR89

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.0080
DANN	Benign	0.48
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.96	T
PhyloP100		-0.68
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.035
Sift	Benign	0.60	T
Sift4G	Benign	0.37	T
PromoterAI		-0.015	Neutral
gMVP		0.20
Mutation Taster		=97/3	polymorphism

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

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

Other links and lift over

hg19: chr10-81319215;