10-79557308-A-G

Variant names:

• chr10-79557308-A-G
• rs17096771
• NM_001098668.4:c.648T>C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001098668.4(SFTPA2):​c.648T>C​(p.Pro216Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000919 in 1,610,236 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00083 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00093 (15 hom.)
• Consequence: SFTPA2 NM_001098668.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.35
• Publications: 4 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 Submitted by: ClinGen
• interstitial lung disease 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• idiopathic pulmonary fibrosis

  Inheritance: Unknown, AD Classification: MODERATE, LIMITED Submitted by: Laboratory for Molecular Medicine, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 10-79557308-A-G is Benign according to our data. Variant chr10-79557308-A-G is described in ClinVar as Benign. ClinVar VariationId is 227070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.35 with no splicing effect.
• BS2: High AC in GnomAd4 at 124 AD,Unknown gene.

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.648T>C	p.Pro216Pro	synonymous	Exon 6 of 6	NP_001092138.1	Q8IWL1
	SFTPA2	NM_001320814.1		c.678T>C	p.Pro226Pro	synonymous	Exon 5 of 5	NP_001307743.1
	SFTPA2	NM_001320813.2		c.648T>C	p.Pro216Pro	synonymous	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.648T>C	p.Pro216Pro	synonymous	Exon 6 of 6	ENSP00000361400.2	Q8IWL1
	SFTPA2	ENST00000372327.9	TSL:1	c.648T>C	p.Pro216Pro	synonymous	Exon 5 of 5	ENSP00000361402.5	Q8IWL1
	SFTPA2	ENST00000959071.1		c.777T>C	p.Pro259Pro	synonymous	Exon 6 of 6	ENSP00000629130.1

Frequencies

GnomAD3 genomes AF: 0.000834 AC: 125 AN: 149908 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000596

Gnomad ASJ AF: 0.000294

Gnomad EAS AF: 0.000786

Gnomad SAS AF: 0.0138

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000537

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000797 AC: 200 AN: 250946 AF XY: 0.000937

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.000326

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000158

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000929 AC: 1356 AN: 1460200 Hom.: 15 Cov.: 34 AF XY: 0.00116 AC XY: 842 AN XY: 726314

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000120 AC: 4 AN: 33436

American (AMR) AF: 0.000515 AC: 23 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.000191 AC: 5 AN: 26130

East Asian (EAS) AF: 0.000378 AC: 15 AN: 39690

South Asian (SAS) AF: 0.00974 AC: 836 AN: 85814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5760

European-Non Finnish (NFE) AF: 0.000365 AC: 405 AN: 1110986

Other (OTH) AF: 0.00106 AC: 64 AN: 60322

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000826 AC: 124 AN: 150036 Hom.: 1 Cov.: 31 AF XY: 0.000980 AC XY: 72 AN XY: 73460

African (AFR) AF: 0.000244 AC: 10 AN: 40920

American (AMR) AF: 0.000596 AC: 9 AN: 15110

Ashkenazi Jewish (ASJ) AF: 0.000294 AC: 1 AN: 3406

East Asian (EAS) AF: 0.000787 AC: 4 AN: 5080

South Asian (SAS) AF: 0.0136 AC: 64 AN: 4718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.000537 AC: 36 AN: 67010

Other (OTH) AF: 0.00 AC: 0 AN: 2068

Alfa AF: 0.000718 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.55
PhyloP100		-1.4
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs17096771; hg19: chr10-81317064; COSMIC: COSV64882209; COSMIC: COSV64882209;