Variant 20-35975958-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001365709.1(CNBD2):c.199C>G(p.Gln67Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CNBD2
NM_001365709.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.421

Variant links:

Genes affected

CNBD2 (HGNC:16145): (cyclic nucleotide binding domain containing 2) Predicted to enable cAMP binding activity. Predicted to be involved in spermatogenesis. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

CNBD2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.102645695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNBD2	NM_001365709.1 linkuse as main transcript	c.199C>G	p.Gln67Glu	missense_variant	3/12	ENST00000373973.7	NP_001352638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNBD2	ENST00000373973.7 linkuse as main transcript	c.199C>G	p.Gln67Glu	missense_variant	3/12	5	NM_001365709.1	ENSP00000363084	A2	Q96M20-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251402

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135860

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460642

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726590

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Mar 16, 2022

The c.199C>G (p.Q67E) alteration is located in exon 3 (coding exon 3) of the CNBD2 gene. This alteration results from a C to G substitution at nucleotide position 199, causing the glutamine (Q) at amino acid position 67 to be replaced by a glutamic acid (E). 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

0.081

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.2

DANN

Benign

0.95

DEOGEN2

Benign

0.022

.;T;.;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.70

T;T;T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.10

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;L;L;L

MutationTaster

Benign

0.96

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.85

.;N;N;N

REVEL

Benign

0.053

Sift

Benign

0.13

.;T;T;T

Sift4G

Benign

0.10

T;T;T;T

Polyphen

0.028, 0.047

.;B;B;.

Vest4

0.25, 0.24, 0.28

MutPred

0.52

.;Gain of ubiquitination at K65 (P = 0.0357);Gain of ubiquitination at K65 (P = 0.0357);Gain of ubiquitination at K65 (P = 0.0357);

MVP

0.15

MPC

0.13

ClinPred

0.090

GERP RS

3.9

Varity_R

0.12

gMVP

0.23

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over