Genetic Variant SFTPA2:c.*152C>A (chr10-79557057-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001098668.4(SFTPA2):c.*152C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000269 in 1,115,522 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SFTPA2
NM_001098668.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0530

Publications

0 publications found

Variant links:

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

SFTPA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SFTPA2	NM_001098668.4	MANE Select	c.*152C>A	3_prime_UTR	Exon 6 of 6	NP_001092138.1	Q8IWL1
SFTPA2	NM_001320814.1		c.*152C>A	3_prime_UTR	Exon 5 of 5	NP_001307743.1
SFTPA2	NM_001320813.2		c.*152C>A	3_prime_UTR	Exon 6 of 6	NP_001307742.1	Q8IWL1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SFTPA2	ENST00000372325.7	TSL:1 MANE Select	c.*152C>A	3_prime_UTR	Exon 6 of 6	ENSP00000361400.2	Q8IWL1
SFTPA2	ENST00000959071.1		c.*152C>A	3_prime_UTR	Exon 6 of 6	ENSP00000629130.1
SFTPA2	ENST00000905087.1		c.*152C>A	3_prime_UTR	Exon 6 of 6	ENSP00000575146.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000269

AC:

AN:

1115522

Hom.:

Cov.:

AF XY:

0.00000541

AC XY:

AN XY:

554602

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26010

American (AMR)

AF:

0.00

AC:

AN:

31126

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19992

East Asian (EAS)

AF:

0.00

AC:

AN:

34804

South Asian (SAS)

AF:

0.0000461

AC:

AN:

65118

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43686

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4382

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

842466

Other (OTH)

AF:

0.00

AC:

AN:

47938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.0

(source)

DANN

Benign

0.54

PhyloP100

0.053

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over