rs121917738

chr10-79557363-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1 PM2 PP3_Strong PP5

The NM_001098668.4(SFTPA2):c.593T>C(p.Phe198Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SFTPA2 NM_001098668.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.62

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 Likely_pathogenic. Variant got 9 ACMG points.

• PM1: In a domain C-type lectin (size 116) in uniprot entity SFPA2_HUMAN there are 18 pathogenic changes around while only 1 benign (95%) in NM_001098668.4
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.993
• PP5: Variant 10-79557363-A-G is Pathogenic according to our data. Variant chr10-79557363-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 13200.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr10-79557363-A-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPA2	NM_001098668.4	c.593T>C	p.Phe198Ser	missense_variant	6/6	ENST00000372325.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPA2	ENST00000372325.7	c.593T>C	p.Phe198Ser	missense_variant	6/6	1	NM_001098668.4	P1
SFTPA2	ENST00000372327.9	c.593T>C	p.Phe198Ser	missense_variant	5/5	1		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Interstitial lung disease 2 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 01, 2009

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Uncertain	0.33
Eigen_PC	Benign	0.016
FATHMM_MKL	Benign	0.44	N
M_CAP	Benign	0.0088	T
MetaRNN	Pathogenic	0.99	D;D
MetaSVM	Uncertain	0.28	D
MutationTaster	Benign	0.00083	A;A
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-7.6	D;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0040	D;D
Sift4G	Pathogenic	0.0010	D;D
Vest4		0.93
MutPred		0.91		Gain of glycosylation at F198 (P = 0.0055);Gain of glycosylation at F198 (P = 0.0055);
MVP		0.65
MPC		2.8
ClinPred		0.98	D
GERP RS		2.8
gMVP		0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs121917738; hg19: chr10-81317119;