Variant 20-35984676-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001365709.1(CNBD2):c.614T>C(p.Met205Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,614,122 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CNBD2
NM_001365709.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.40

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 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
CNBD2	NM_001365709.1 linkuse as main transcript	c.614T>C	p.Met205Thr	missense_variant	6/12	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.614T>C	p.Met205Thr	missense_variant	6/12	5	NM_001365709.1	ENSP00000363084	A2	Q96M20-1
CNBD2	ENST00000538900.1 linkuse as main transcript	c.614T>C	p.Met205Thr	missense_variant	6/11	1		ENSP00000442729	P2	Q96M20-3
CNBD2	ENST00000463258.6 linkuse as main transcript	c.*22T>C		3_prime_UTR_variant, NMD_transcript_variant	5/9	1		ENSP00000476014
CNBD2	ENST00000349339.5 linkuse as main transcript	c.614T>C	p.Met205Thr	missense_variant	6/12	2		ENSP00000340954	A2	Q96M20-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727238

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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 23, 2023

The c.614T>C (p.M205T) alteration is located in exon 6 (coding exon 6) of the CNBD2 gene. This alteration results from a T to C substitution at nucleotide position 614, causing the methionine (M) at amino acid position 205 to be replaced by a threonine (T). 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

Pathogenic

0.61

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

T;.;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.76

T;T;T

M_CAP

Benign

0.045

MetaRNN

Uncertain

0.49

T;T;T

MetaSVM

Uncertain

0.58

MutationAssessor

Uncertain

2.2

M;M;M

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Pathogenic

0.69

Sift

Benign

0.030

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

0.89

P;D;.

Vest4

0.60

MutPred

0.38

Gain of phosphorylation at T201 (P = 0.1034);Gain of phosphorylation at T201 (P = 0.1034);Gain of phosphorylation at T201 (P = 0.1034);

MVP

0.62

MPC

0.21

ClinPred

0.94

GERP RS

4.9

Varity_R

0.41

gMVP

0.53

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

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