10-79557350-A-G

Variant names:

• chr10-79557350-A-G
• rs17880902
• NM_001098668.4:c.606T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001098668.4(SFTPA2):​c.606T>C​(p.Asp202Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00374 in 150,796 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (11 hom.)
  • Failed GnomAD Quality Control
• Consequence: SFTPA2 NM_001098668.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.231
• 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, 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 10-79557350-A-G is Benign according to our data. Variant chr10-79557350-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2640641.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.231 with no splicing effect.
• BS2: High AC in GnomAd4 at 564 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.606T>C	p.Asp202Asp	synonymous	Exon 6 of 6	NP_001092138.1
	SFTPA2	NM_001320814.1		c.636T>C	p.Asp212Asp	synonymous	Exon 5 of 5	NP_001307743.1
	SFTPA2	NM_001320813.2		c.606T>C	p.Asp202Asp	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.606T>C	p.Asp202Asp	synonymous	Exon 6 of 6	ENSP00000361400.2
	SFTPA2	ENST00000372327.9	TSL:1	c.606T>C	p.Asp202Asp	synonymous	Exon 5 of 5	ENSP00000361402.5
	SFTPA2	ENST00000959071.1		c.735T>C	p.Asp245Asp	synonymous	Exon 6 of 6	ENSP00000629130.1

Frequencies

GnomAD3 genomes AF: 0.00369 AC: 556 AN: 150676 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00559

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00218

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.000783

Gnomad SAS AF: 0.00105

Gnomad FIN AF: 0.000568

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00405

Gnomad OTH AF: 0.00242

GnomAD2 exomes AF: 0.000786 AC: 197 AN: 250760 AF XY: 0.000686

Gnomad AFR exome AF: 0.00241

Gnomad AMR exome AF: 0.000782

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.0000925

Gnomad NFE exome AF: 0.000900

Gnomad OTH exome AF: 0.00114

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00120 AC: 1751 AN: 1454642 Hom.: 11 Cov.: 34 AF XY: 0.00120 AC XY: 870 AN XY: 723826

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

African (AFR) AF: 0.00231 AC: 77 AN: 33292

American (AMR) AF: 0.000986 AC: 44 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26134

East Asian (EAS) AF: 0.000327 AC: 13 AN: 39696

South Asian (SAS) AF: 0.000929 AC: 80 AN: 86124

European-Finnish (FIN) AF: 0.000956 AC: 51 AN: 53374

Middle Eastern (MID) AF: 0.00209 AC: 12 AN: 5740

European-Non Finnish (NFE) AF: 0.00125 AC: 1380 AN: 1105452

Other (OTH) AF: 0.00151 AC: 91 AN: 60194

⚠️ 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: 0.00374 AC: 564 AN: 150796 Hom.: 1 Cov.: 31 AF XY: 0.00359 AC XY: 265 AN XY: 73860

African (AFR) AF: 0.00579 AC: 238 AN: 41108

American (AMR) AF: 0.00217 AC: 33 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.000290 AC: 1 AN: 3446

East Asian (EAS) AF: 0.000785 AC: 4 AN: 5098

South Asian (SAS) AF: 0.000841 AC: 4 AN: 4758

European-Finnish (FIN) AF: 0.000568 AC: 6 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00405 AC: 273 AN: 67368

Other (OTH) AF: 0.00240 AC: 5 AN: 2084

Alfa AF: 0.00350 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.45
DANN	Benign	0.26
PhyloP100		-0.23
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: rs17880902; hg19: chr10-81317106;