19-48470496-GGC-TCT

Variant names:

• chr19-48470496-GGC-TCT
• NM_004228.7:c.163_165delGGCinsTCT
• CYTH2 p.Gly55Ser

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_004228.7(CYTH2):​c.163_165delGGCinsTCT​(p.Gly55Ser) variant causes a missense, splice region change. 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 MNV, 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CYTH2 NM_004228.7 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.59
• Publications: 0 publications found

Genes affected

CYTH2 (HGNC:9502): (cytohesin 2) The protein encoded by this gene is a member of the PSCD family. Members of this family have identical structural organization that consists of an N-terminal coiled-coil motif, a central Sec7 domain, and a C-terminal pleckstrin homology (PH) domain. The coiled-coil motif is involved in homodimerization, the Sec7 domain contains guanine-nucleotide exchange protein (GEP) activity, and the PH domain interacts with phospholipids and is responsible for association of PSCDs with membranes. Members of this family appear to mediate the regulation of protein sorting and membrane trafficking. The encoded protein exhibits GEP activity in vitro with ARF1, ARF3, and ARF6 and is 83% homologous to CYTH1. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

ENSG00000268465 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004228.7. 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
	CYTH2	NM_004228.7	MANE Select	c.163_165delGGCinsTCT	p.Gly55Ser	missense splice_region	N/A	NP_004219.3
	CYTH2	NM_017457.6		c.163_165delGGCinsTCT	p.Gly55Ser	missense splice_region	N/A	NP_059431.1	Q99418-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYTH2	ENST00000452733.7	TSL:1 MANE Select	c.163_165delGGCinsTCT	p.Gly55Ser	missense splice_region	N/A	ENSP00000408236.2	Q99418-2
	CYTH2	ENST00000427476.4	TSL:1	c.163_165delGGCinsTCT	p.Gly55Ser	missense splice_region	N/A	ENSP00000486578.1	A0A0D9SFG6
	ENSG00000268465	ENST00000595676.1	TSL:2	c.115_117delGGCinsTCT	p.Gly39Ser	missense splice_region	N/A	ENSP00000470383.1	M0QZ92

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.6

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-48973753;