ENST00000381529.9:c.728_729insGTCGGTGAGACAGAAAG

Variant names:

• chrX-1294409-A-AGTCGGTGAGACAGAAAG
• NM_172245.4:c.728_729insGTCGGTGAGACAGAAAG

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1

The ENST00000381529.9(CSF2RA):​c.728_729insGTCGGTGAGACAGAAAG​(p.Tyr243fs) variant causes a frameshift, stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSF2RA ENST00000381529.9 frameshift, stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• Publications: 0 publications found

Genes affected

CSF2RA (HGNC:2435): (colony stimulating factor 2 receptor subunit alpha) The protein encoded by this gene is the alpha subunit of the heterodimeric receptor for colony stimulating factor 2, a cytokine which controls the production, differentiation, and function of granulocytes and macrophages. The encoded protein is a member of the cytokine family of receptors. This gene is found in the pseudoautosomal region (PAR) of the X and Y chromosomes. Multiple transcript variants encoding different isoforms have been found for this gene, with some of the isoforms being membrane-bound and others being soluble. [provided by RefSeq, Jul 2008]

CSF2RA Gene-Disease associations (from GenCC):

• surfactant metabolism dysfunction, pulmonary, 4

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• hereditary pulmonary alveolar proteinosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000381529.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RA	NM_172245.4	MANE Select	c.728_729insGTCGGTGAGACAGAAAG	p.Tyr243fs	frameshift stop_gained	Exon 8 of 13	NP_758448.1
	CSF2RA	NM_001161530.2		c.728_729insGTCGGTGAGACAGAAAG	p.Tyr243fs	frameshift stop_gained	Exon 8 of 14	NP_001155002.1
	CSF2RA	NM_001379153.1		c.728_729insGTCGGTGAGACAGAAAG	p.Tyr243fs	frameshift stop_gained	Exon 7 of 13	NP_001366082.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RA	ENST00000381529.9	TSL:1 MANE Select	c.728_729insGTCGGTGAGACAGAAAG	p.Tyr243fs	frameshift stop_gained	Exon 8 of 13	ENSP00000370940.3
	CSF2RA	ENST00000381509.8	TSL:1	c.728_729insGTCGGTGAGACAGAAAG	p.Tyr243fs	frameshift stop_gained	Exon 8 of 13	ENSP00000370920.3
	CSF2RA	ENST00000381524.8	TSL:1	c.728_729insGTCGGTGAGACAGAAAG	p.Tyr243fs	frameshift stop_gained	Exon 8 of 13	ENSP00000370935.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.0

Splicing

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

Other links and lift over

hg19: chrX-1413302;