20-35980501-C-T

Variant names:

• chr20-35980501-C-T
• rs184047696
• NM_001365709.1:c.286C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001365709.1(CNBD2):​c.286C>T​(p.Pro96Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,860 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. P96A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CNBD2 NM_001365709.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.04
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365709.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNBD2	NM_001365709.1	MANE Select	c.286C>T	p.Pro96Ser	missense	Exon 4 of 12	NP_001352638.1	Q96M20-1
	CNBD2	NM_080834.4		c.286C>T	p.Pro96Ser	missense	Exon 4 of 12	NP_543024.2	Q96M20-2
	CNBD2	NM_001207076.3		c.286C>T	p.Pro96Ser	missense	Exon 4 of 11	NP_001194005.1	Q96M20-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNBD2	ENST00000373973.7	TSL:5 MANE Select	c.286C>T	p.Pro96Ser	missense	Exon 4 of 12	ENSP00000363084.3	Q96M20-1
	CNBD2	ENST00000538900.1	TSL:1	c.286C>T	p.Pro96Ser	missense	Exon 4 of 11	ENSP00000442729.1	Q96M20-3
	CNBD2	ENST00000463258.6	TSL:1	n.286C>T		non_coding_transcript_exon	Exon 4 of 9	ENSP00000476014.1	U3KQM1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727236

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111982

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Uncertain	0.55	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		5.0
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.37
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.66
MutPred		0.42		Gain of disorder (P = 0.0755)
MVP		0.71
MPC		0.55
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.63
gMVP		0.47
Mutation Taster		=66/34	polymorphism

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

Other links and lift over

dbSNP: rs184047696; hg19: chr20-34568423;