rs121917737
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PM5PP3_StrongPP5
The NM_001098668.4(SFTPA2):c.692G>T(p.Gly231Val) 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 Likely risk allele (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G231R) has been classified as Likely pathogenic.
Frequency
Genomes: not found (cov: 32)
Consequence
SFTPA2
NM_001098668.4 missense
NM_001098668.4 missense
Scores
6
7
3
Clinical Significance
Conservation
PhyloP100: 3.94
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PM1
?
In a disulfide_bond (size 14) in uniprot entity SFPA2_HUMAN there are 8 pathogenic changes around while only 0 benign (100%) in NM_001098668.4
PM2
?
Very rare variant in population databases, with high coverage;
PM5
?
Other missense variant is known to change same aminoacid residue: Variant chr10-79557265-C-T is described in Lovd as [Likely_pathogenic].
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.986
PP5
?
Variant 10-79557264-C-A is Pathogenic according to our data. Variant chr10-79557264-C-A is described in ClinVar as [Likely_risk_allele]. Clinvar id is 13199.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_pathogenic, oryginal submission is: [Likely_risk_allele]. Variant chr10-79557264-C-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SFTPA2 | NM_001098668.4 | c.692G>T | p.Gly231Val | missense_variant | 6/6 | ENST00000372325.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SFTPA2 | ENST00000372325.7 | c.692G>T | p.Gly231Val | missense_variant | 6/6 | 1 | NM_001098668.4 | P1 | |
SFTPA2 | ENST00000372327.9 | c.692G>T | p.Gly231Val | missense_variant | 5/5 | 1 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Bravo
AF:
ClinVar
Significance: Pathogenic/Likely risk allele
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Interstitial lung disease 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 2009 | - - |
Pulmonary fibrosis Pathogenic:1
Likely risk allele, no assertion criteria provided | research | Garcia Pulmonary Genetics Research Laboratory, Columbia University Irving Medical Center | Jun 09, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
A;A
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Vest4
MutPred
Gain of solvent accessibility (P = 0.0713);Gain of solvent accessibility (P = 0.0713);
MVP
MPC
ClinPred
D
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at