Genetic Variant CYTH2:p.Glu365Gln (chr19-48478573-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_004228.7(CYTH2):c.1093G>C(p.Glu365Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000151 in 1,460,576 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E365K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

CYTH2
NM_004228.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.65

Publications

0 publications found

Variant links:

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]

CYTH2 links:

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ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYTH2	NM_004228.7 link	c.1093G>C	p.Glu365Gln	missense_variant	Exon 11 of 12	ENST00000452733.7	NP_004219.3	Q99418-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYTH2	ENST00000452733.7 link	c.1093G>C	p.Glu365Gln	missense_variant	Exon 11 of 12	1	NM_004228.7	ENSP00000408236.2		Q99418-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000201

AC:

AN:

249318

AF XY:

0.0000223

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1460576

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726522

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44636

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26042

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.000232

AC:

AN:

86096

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53248

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111316

Other (OTH)

AF:

0.0000166

AC:

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.030

.;T;T

Eigen

Benign

-0.0097

Eigen_PC

Benign

0.099

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

T;T;T

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.56

D;D;D

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.0

.;.;L

PhyloP100

6.7

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.9

N;.;.

REVEL

Uncertain

0.39

Sift

Benign

0.28

T;.;.

Sift4G

Benign

0.28

T;T;.

Polyphen

0.23

B;.;.

Vest4

0.45

MutPred

0.45

Gain of methylation at K368 (P = 0.0806);.;.;

MVP

0.80

MPC

0.83

ClinPred

0.52

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.30

gMVP

0.82

Mutation Taster

=79/21

polymorphism

(source)

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

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19-48478573-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over