17-4969643-C-T

Position:

• chr17-4969643-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_015099.4(CAMTA2):​c.3248G>A​(p.Arg1083Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,848 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: 0.000012 (0 hom.)
• Consequence: CAMTA2 NM_015099.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.56

Genes affected

CAMTA2 (HGNC:18807): (calmodulin binding transcription activator 2) The protein encoded by this gene is a member of the calmodulin-binding transcription activator protein family. Members of this family share a common domain structure that consists of a transcription activation domain, a DNA-binding domain, and a calmodulin-binding domain. The encoded protein may be a transcriptional coactivator of genes involved in cardiac growth. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMTA2	NM_015099.4	c.3248G>A	p.Arg1083Gln	missense_variant	19/23	ENST00000348066.8	NP_055914.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMTA2	ENST00000348066.8	c.3248G>A	p.Arg1083Gln	missense_variant	19/23	1	NM_015099.4	ENSP00000321813	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1461848 Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8 AN XY: 727230

Gnomad4 AFR exome AF: 0.0000299

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: 0.0000144

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2021

The c.3317G>A (p.R1106Q) alteration is located in exon 19 (coding exon 19) of the CAMTA2 gene. This alteration results from a G to A substitution at nucleotide position 3317, causing the arginine (R) at amino acid position 1106 to be replaced by a glutamine (Q). 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	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	34
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.26	.;.;T;.;D
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Pathogenic	1.0	D;D;D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.59	D;D;D;D;D
MetaSVM	Uncertain	0.15	D
MutationAssessor	Uncertain	2.6	.;.;.;.;M
MutationTaster	Benign	0.99	D;D;D;D;D;D
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-3.6	D;D;.;D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D;D;.;D;D
Sift4G	Uncertain	0.0070	D;D;D;D;D
Polyphen		1.0, 0.27, 1.0	.;D;.;B;D
Vest4		0.71
MVP		0.96
MPC		2.1
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.68
gMVP		0.99

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

Other links and lift over

dbSNP: rs1252243327; hg19: chr17-4872938; COSMIC: COSV99236293; COSMIC: COSV99236293;