chr10-79557057-G-A

Variant names:

• chr10-79557057-G-A
• rs9408
• NM_001098668.4:c.*152C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001098668.4(SFTPA2):​c.*152C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0755 in 1,265,498 control chromosomes in the GnomAD database, including 4,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.073 (559 hom., cov: 32)
  • Exomes 𝑓: 0.076 (3964 hom.)
• Consequence: SFTPA2 NM_001098668.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0530
• Publications: 6 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: 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 10-79557057-G-A is Benign according to our data. Variant chr10-79557057-G-A is described in ClinVar as Benign. ClinVar VariationId is 1258839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

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.*152C>T		3_prime_UTR	Exon 6 of 6	NP_001092138.1	Q8IWL1
	SFTPA2	NM_001320814.1		c.*152C>T		3_prime_UTR	Exon 5 of 5	NP_001307743.1
	SFTPA2	NM_001320813.2		c.*152C>T		3_prime_UTR	Exon 6 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.*152C>T		3_prime_UTR	Exon 6 of 6	ENSP00000361400.2	Q8IWL1
	SFTPA2	ENST00000959071.1		c.*152C>T		3_prime_UTR	Exon 6 of 6	ENSP00000629130.1
	SFTPA2	ENST00000905087.1		c.*152C>T		3_prime_UTR	Exon 6 of 6	ENSP00000575146.1

Frequencies

GnomAD3 genomes AF: 0.0731 AC: 11106 AN: 151978 Hom.: 558 Cov.: 32

Gnomad AFR AF: 0.0409

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0673

Gnomad ASJ AF: 0.0916

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.0704

Gnomad FIN AF: 0.0728

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0766

Gnomad OTH AF: 0.0807

GnomAD4 exome AF: 0.0759 AC: 84464 AN: 1113402 Hom.: 3964 Cov.: 16 AF XY: 0.0756 AC XY: 41862 AN XY: 553626

African (AFR) AF: 0.0392 AC: 1020 AN: 25990

American (AMR) AF: 0.0446 AC: 1385 AN: 31040

Ashkenazi Jewish (ASJ) AF: 0.0905 AC: 1806 AN: 19962

East Asian (EAS) AF: 0.247 AC: 8575 AN: 34774

South Asian (SAS) AF: 0.0663 AC: 4311 AN: 65004

European-Finnish (FIN) AF: 0.0787 AC: 3436 AN: 43660

Middle Eastern (MID) AF: 0.0642 AC: 281 AN: 4376

European-Non Finnish (NFE) AF: 0.0709 AC: 59576 AN: 840736

Other (OTH) AF: 0.0851 AC: 4074 AN: 47860

GnomAD4 genome AF: 0.0732 AC: 11131 AN: 152096 Hom.: 559 Cov.: 32 AF XY: 0.0745 AC XY: 5541 AN XY: 74348

African (AFR) AF: 0.0411 AC: 1706 AN: 41490

American (AMR) AF: 0.0673 AC: 1028 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0916 AC: 318 AN: 3472

East Asian (EAS) AF: 0.284 AC: 1462 AN: 5156

South Asian (SAS) AF: 0.0710 AC: 342 AN: 4814

European-Finnish (FIN) AF: 0.0728 AC: 771 AN: 10588

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0766 AC: 5207 AN: 67982

Other (OTH) AF: 0.0841 AC: 177 AN: 2104

Alfa AF: 0.0706 Hom.: 58

Bravo AF: 0.0723

Asia WGS AF: 0.177 AC: 614 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.44
PhyloP100		0.053
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9408; hg19: chr10-81316813; COSMIC: COSV64882393; COSMIC: COSV64882393;