NM_001098668.4:c.271G>C

Variant names:

• chr10-79558907-C-G
• rs17886395
• NM_001098668.4:c.271G>C

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.271G>C​(p.Ala91Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,613,720 control chromosomes in the GnomAD database, including 21,037 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2363 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18674 hom.)
• Consequence: SFTPA2 NM_001098668.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0340
• Publications: 53 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 (MetaRNN=0.018847167).
• BP6: Variant 10-79558907-C-G is Benign according to our data. Variant chr10-79558907-C-G is described in ClinVar as Benign. ClinVar VariationId is 227067.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.27 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.271G>C	p.Ala91Pro	missense	Exon 4 of 6	NP_001092138.1	Q8IWL1
	SFTPA2	NM_001320814.1		c.301G>C	p.Ala101Pro	missense	Exon 3 of 5	NP_001307743.1
	SFTPA2	NM_001320813.2		c.271G>C	p.Ala91Pro	missense	Exon 4 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.271G>C	p.Ala91Pro	missense	Exon 4 of 6	ENSP00000361400.2	Q8IWL1
	SFTPA2	ENST00000372327.9	TSL:1	c.271G>C	p.Ala91Pro	missense	Exon 3 of 5	ENSP00000361402.5	Q8IWL1
	SFTPA2	ENST00000959071.1		c.271G>C	p.Ala91Pro	missense	Exon 4 of 6	ENSP00000629130.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25407 AN: 151868 Hom.: 2350 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.183

GnomAD2 exomes AF: 0.189 AC: 47412 AN: 251402 AF XY: 0.188

Gnomad AFR exome AF: 0.168

Gnomad AMR exome AF: 0.283

Gnomad ASJ exome AF: 0.147

Gnomad EAS exome AF: 0.295

Gnomad FIN exome AF: 0.136

Gnomad NFE exome AF: 0.143

Gnomad OTH exome AF: 0.178

GnomAD4 exome AF: 0.153 AC: 223882 AN: 1461732 Hom.: 18674 Cov.: 70 AF XY: 0.156 AC XY: 113246 AN XY: 727174

African (AFR) AF: 0.164 AC: 5504 AN: 33468

American (AMR) AF: 0.278 AC: 12423 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 3857 AN: 26136

East Asian (EAS) AF: 0.257 AC: 10197 AN: 39696

South Asian (SAS) AF: 0.252 AC: 21706 AN: 86258

European-Finnish (FIN) AF: 0.138 AC: 7358 AN: 53406

Middle Eastern (MID) AF: 0.184 AC: 1062 AN: 5762

European-Non Finnish (NFE) AF: 0.136 AC: 151769 AN: 1111890

Other (OTH) AF: 0.166 AC: 10006 AN: 60392

GnomAD4 genome AF: 0.168 AC: 25474 AN: 151988 Hom.: 2363 Cov.: 32 AF XY: 0.172 AC XY: 12745 AN XY: 74306

African (AFR) AF: 0.169 AC: 6998 AN: 41430

American (AMR) AF: 0.244 AC: 3727 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 516 AN: 3466

East Asian (EAS) AF: 0.282 AC: 1448 AN: 5134

South Asian (SAS) AF: 0.271 AC: 1304 AN: 4808

European-Finnish (FIN) AF: 0.124 AC: 1315 AN: 10598

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.142 AC: 9653 AN: 67958

Other (OTH) AF: 0.190 AC: 400 AN: 2110

Alfa AF: 0.151 Hom.: 586

Bravo AF: 0.174

TwinsUK AF: 0.128 AC: 474

ALSPAC AF: 0.134 AC: 517

ESP6500AA AF: 0.162 AC: 713

ESP6500EA AF: 0.143 AC: 1226

ExAC AF: 0.186 AC: 22544

Asia WGS AF: 0.302 AC: 1047 AN: 3478

EpiCase AF: 0.145

EpiControl AF: 0.144

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	SFTPA2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.046
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	6.0
DANN	Benign	0.066
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00015	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.034
PrimateAI	Benign	0.47	T
PROVEAN	Benign	2.7	N
REVEL	Benign	0.17
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.13
MPC		0.0036
ClinPred		0.00058	T
GERP RS		1.6
gMVP		0.21
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: rs17886395; hg19: chr10-81318663; COSMIC: COSV64882320; COSMIC: COSV64882320;