10-79557350-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001098668.4(SFTPA2):c.606T>C(p.Asp202=) 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

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]

ACMG classification

Verdict is Benign. Variant got -15 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 id is 2640641.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.231 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00374 (564/150796) while in subpopulation AFR AF= 0.00579 (238/41108). AF 95% confidence interval is 0.00519. There are 1 homozygotes in gnomad4. There are 265 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 556 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPA2	NM_001098668.4	c.606T>C	p.Asp202=	synonymous_variant	6/6	ENST00000372325.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPA2	ENST00000372325.7	c.606T>C	p.Asp202=	synonymous_variant	6/6	1	NM_001098668.4	P1
SFTPA2	ENST00000372327.9	c.606T>C	p.Asp202=	synonymous_variant	5/5	1		P1

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

GnomAD3 exomes AF: 0.000786 AC: 197 AN: 250760 Hom.: 4 AF XY: 0.000686 AC XY: 93 AN XY: 135556

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 SAS exome AF: 0.000523

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

Gnomad4 AFR exome AF: 0.00231

Gnomad4 AMR exome AF: 0.000986

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.000327

Gnomad4 SAS exome AF: 0.000929

Gnomad4 FIN exome AF: 0.000956

Gnomad4 NFE exome AF: 0.00125

Gnomad4 OTH exome AF: 0.00151

GnomAD4 genome AF: 0.00374 AC: 564 AN: 150796 Hom.: 1 Cov.: 31 AF XY: 0.00359 AC XY: 265 AN XY: 73860

Gnomad4 AFR AF: 0.00579

Gnomad4 AMR AF: 0.00217

Gnomad4 ASJ AF: 0.000290

Gnomad4 EAS AF: 0.000785

Gnomad4 SAS AF: 0.000841

Gnomad4 FIN AF: 0.000568

Gnomad4 NFE AF: 0.00405

Gnomad4 OTH AF: 0.00240

Alfa AF: 0.00350 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

SFTPA2: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.45
Dann	Benign	0.26

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

Publications

LitVar

Other links and lift over

dbSNP: rs17880902; hg19: chr10-81317106;