19-48469282-A-T

Variant names:

• chr19-48469282-A-T
• rs1799257
• ENST00000427476.4:c.-226A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000427476.4(CYTH2):​c.-226A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYTH2 ENST00000427476.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 13 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000427476.4. 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
	LOC105372430	NR_186576.1		n.252T>A		non_coding_transcript_exon	Exon 1 of 3
	CYTH2	NM_004228.7	MANE Select	c.-226A>T		upstream_gene	N/A	NP_004219.3
	CYTH2	NM_017457.6		c.-226A>T		upstream_gene	N/A	NP_059431.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYTH2	ENST00000427476.4	TSL:1	c.-226A>T		5_prime_UTR	Exon 1 of 12	ENSP00000486578.1
	ENSG00000268465	ENST00000595676.1	TSL:2	c.-29-1071A>T		intron	N/A	ENSP00000470383.1
	ENSG00000268530	ENST00000593476.1	TSL:1	n.264+148T>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 264176 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 133740

African (AFR) AF: 0.00 AC: 0 AN: 7326

American (AMR) AF: 0.00 AC: 0 AN: 7286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9234

East Asian (EAS) AF: 0.00 AC: 0 AN: 22718

South Asian (SAS) AF: 0.00 AC: 0 AN: 3168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1324

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 175850

Other (OTH) AF: 0.00 AC: 0 AN: 16754

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 131735

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.48
PhyloP100		1.2
PromoterAI		-0.024	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1799257; hg19: chr19-48972539;