Variant chr7-29496012-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004067.4(CHN2):c.715A>G(p.Ile239Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,540 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CHN2
NM_004067.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.50

Variant links:

Genes affected

CHN2 (HGNC:1944): (chimerin 2) This gene encodes a guanosine triphosphate (GTP)-metabolizing protein that contains a phorbol-ester/diacylglycerol (DAG)-type zinc finger, a Rho-GAP domain, and an SH2 domain. The encoded protein translocates from the cytosol to the Golgi apparatus membrane upon binding by diacylglycerol (DAG). Activity of this protein is important in cell proliferation and migration, and expression changes in this gene have been detected in cancers. A mutation in this gene has also been associated with schizophrenia in men. Alternative transcript splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, May 2014]

CHN2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHN2	NM_004067.4 linkuse as main transcript	c.715A>G	p.Ile239Val	missense_variant	8/13	ENST00000222792.11	NP_004058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHN2	ENST00000222792.11 linkuse as main transcript	c.715A>G	p.Ile239Val	missense_variant	8/13	1	NM_004067.4	ENSP00000222792	P1	P52757-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460540

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726606

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 14, 2024

The c.715A>G (p.I239V) alteration is located in exon 8 (coding exon 8) of the CHN2 gene. This alteration results from a A to G substitution at nucleotide position 715, causing the isoleucine (I) at amino acid position 239 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

.;T;.;.;.;.;.;.

Eigen

Benign

0.077

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D;D;D;D;D;D;D

M_CAP

Benign

0.047

MetaRNN

Uncertain

0.43

T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.10

MutationAssessor

Benign

-0.020

.;N;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;N

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.18

.;N;N;.;N;N;.;N

REVEL

Uncertain

0.47

Sift

Benign

0.40

.;T;T;.;T;T;.;T

Sift4G

Benign

0.20

.;T;T;T;T;D;T;T

Polyphen

0.86, 0.11, 0.59, 0.96

.;P;.;.;B;.;P;D

Vest4

0.41, 0.43, 0.43, 0.41, 0.39, 0.42

MutPred

0.62

Gain of helix (P = 0.0128);.;.;.;.;.;.;.;

MVP

0.88

MPC

0.93

ClinPred

0.92

GERP RS

5.8

Varity_R

0.21

gMVP

0.39

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over