chr2-85668140-G-GGCAGCA

Variant names:

• chr2-85668140-G-GGCAGCA
• rs147057701
• NM_000542.5:c.38_43dupTGCTGC

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP3

The NM_000542.5(SFTPB):​c.38_43dupTGCTGC​(p.Leu13_Leu14dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SFTPB NM_000542.5 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.869
• Publications: 0 publications found

Genes affected

SFTPB (HGNC:10801): (surfactant protein B) This gene encodes the pulmonary-associated surfactant protein B (SPB), an amphipathic surfactant protein essential for lung function and homeostasis after birth. Pulmonary surfactant is a surface-active lipoprotein complex composed of 90% lipids and 10% proteins which include plasma proteins and apolipoproteins SPA, SPB, SPC and SPD. The surfactant is secreted by the alveolar cells of the lung and maintains the stability of pulmonary tissue by reducing the surface tension of fluids that coat the lung. The SPB enhances the rate of spreading and increases the stability of surfactant monolayers in vitro. Multiple mutations in this gene have been identified, which cause pulmonary surfactant metabolism dysfunction type 1, also called pulmonary alveolar proteinosis due to surfactant protein B deficiency, and are associated with fatal respiratory distress in the neonatal period. Alternatively spliced transcript variants encoding the same protein have been identified.[provided by RefSeq, Feb 2010]

SFTPB Gene-Disease associations (from GenCC):

• surfactant metabolism dysfunction, pulmonary, 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_000542.5

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000542.5. 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
	SFTPB	NM_000542.5	MANE Select	c.38_43dupTGCTGC	p.Leu13_Leu14dup	conservative_inframe_insertion	Exon 1 of 11	NP_000533.4
	SFTPB	NM_198843.3		c.38_43dupTGCTGC	p.Leu13_Leu14dup	conservative_inframe_insertion	Exon 2 of 12	NP_942140.3	P07988
	SFTPB	NM_001367281.1		c.38_43dupTGCTGC	p.Leu13_Leu14dup	conservative_inframe_insertion	Exon 1 of 9	NP_001354210.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPB	ENST00000519937.7	TSL:1 MANE Select	c.38_43dupTGCTGC	p.Leu13_Leu14dup	conservative_inframe_insertion	Exon 1 of 11	ENSP00000428719.2	P07988
	SFTPB	ENST00000393822.7	TSL:1	c.38_43dupTGCTGC	p.Leu13_Leu14dup	conservative_inframe_insertion	Exon 2 of 12	ENSP00000377409.4	P07988
	SFTPB	ENST00000409383.7	TSL:1	c.38_43dupTGCTGC	p.Leu13_Leu14dup	conservative_inframe_insertion	Exon 2 of 12	ENSP00000386346.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.87

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs147057701; hg19: chr2-85895263; COSMIC: COSV107425852; COSMIC: COSV107425852;