rs1965707

Variant names:

• chr10-79557536-G-A
• rs1965707
• NM_001098668.4:c.420C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-79557536-G-A
• chr10-79557536-G-C
• chr10-79557536-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001320814.1(SFTPA2):​c.450C>T​(p.Ser150Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,586,620 control chromosomes in the GnomAD database, including 68,001 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7522 hom., cov: 30)
  • Exomes 𝑓: 0.28 (60479 hom.)
• Consequence: SFTPA2 NM_001320814.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.123
• Publications: 22 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, MODERATE Submitted by: Ambry Genetics, ClinGen, 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 10-79557536-G-A is Benign according to our data. Variant chr10-79557536-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 227069.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.123 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320814.1. 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.420C>T	p.Ser140Ser	synonymous	Exon 6 of 6	NP_001092138.1
	SFTPA2	NM_001320814.1		c.450C>T	p.Ser150Ser	synonymous	Exon 5 of 5	NP_001307743.1
	SFTPA2	NM_001320813.2		c.420C>T	p.Ser140Ser	synonymous	Exon 6 of 6	NP_001307742.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPA2	ENST00000372325.7	TSL:1 MANE Select	c.420C>T	p.Ser140Ser	synonymous	Exon 6 of 6	ENSP00000361400.2
	SFTPA2	ENST00000372327.9	TSL:1	c.420C>T	p.Ser140Ser	synonymous	Exon 5 of 5	ENSP00000361402.5
	SFTPA2	ENST00000959071.1		c.549C>T	p.Ser183Ser	synonymous	Exon 6 of 6	ENSP00000629130.1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46323 AN: 150386 Hom.: 7500 Cov.: 30

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.313

GnomAD2 exomes AF: 0.280 AC: 65599 AN: 234178 AF XY: 0.288

Gnomad AFR exome AF: 0.348

Gnomad AMR exome AF: 0.154

Gnomad ASJ exome AF: 0.390

Gnomad EAS exome AF: 0.485

Gnomad FIN exome AF: 0.271

Gnomad NFE exome AF: 0.253

Gnomad OTH exome AF: 0.262

GnomAD4 exome AF: 0.280 AC: 401573 AN: 1436114 Hom.: 60479 Cov.: 36 AF XY: 0.283 AC XY: 202058 AN XY: 713970

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

African (AFR) AF: 0.376 AC: 12296 AN: 32684

American (AMR) AF: 0.169 AC: 7436 AN: 44118

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 10304 AN: 25768

East Asian (EAS) AF: 0.447 AC: 17548 AN: 39232

South Asian (SAS) AF: 0.353 AC: 30078 AN: 85182

European-Finnish (FIN) AF: 0.290 AC: 15171 AN: 52396

Middle Eastern (MID) AF: 0.363 AC: 1959 AN: 5396

European-Non Finnish (NFE) AF: 0.265 AC: 289163 AN: 1091832

Other (OTH) AF: 0.296 AC: 17618 AN: 59506

⚠️ 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: 0.308 AC: 46396 AN: 150506 Hom.: 7522 Cov.: 30 AF XY: 0.309 AC XY: 22696 AN XY: 73494

African (AFR) AF: 0.368 AC: 15006 AN: 40820

American (AMR) AF: 0.222 AC: 3365 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1366 AN: 3458

East Asian (EAS) AF: 0.467 AC: 2378 AN: 5092

South Asian (SAS) AF: 0.334 AC: 1576 AN: 4724

European-Finnish (FIN) AF: 0.273 AC: 2856 AN: 10444

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.279 AC: 18868 AN: 67538

Other (OTH) AF: 0.315 AC: 656 AN: 2082

Alfa AF: 0.316 Hom.: 1424

Bravo AF: 0.307

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Interstitial lung disease 2 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.2
DANN	Benign	0.63
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs1965707; hg19: chr10-81317292; COSMIC: COSV64882330; COSMIC: COSV64882330;