17-4972267-C-T

Variant names:

• chr17-4972267-C-T
• rs367576965
• NM_015099.4:c.2773G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_015099.4(CAMTA2):​c.2773G>A​(p.Asp925Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. D925Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: CAMTA2 NM_015099.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.909
• Publications: 0 publications found

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]

ENSG00000234203 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.062839985).
• BS2: High AC in GnomAd4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015099.4. 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
	CAMTA2	NM_015099.4	MANE Select	c.2773G>A	p.Asp925Asn	missense	Exon 16 of 23	NP_055914.2
	CAMTA2	NM_001171167.2		c.2842G>A	p.Asp948Asn	missense	Exon 16 of 23	NP_001164638.1	O94983-6
	CAMTA2	NM_001171168.2		c.2770G>A	p.Asp924Asn	missense	Exon 15 of 22	NP_001164639.1	O94983-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMTA2	ENST00000348066.8	TSL:1 MANE Select	c.2773G>A	p.Asp925Asn	missense	Exon 16 of 23	ENSP00000321813.7	O94983-1
	CAMTA2	ENST00000414043.7	TSL:1	c.2842G>A	p.Asp948Asn	missense	Exon 16 of 23	ENSP00000412886.3	O94983-6
	CAMTA2	ENST00000361571.9	TSL:1	c.2770G>A	p.Asp924Asn	missense	Exon 15 of 22	ENSP00000354828.5	O94983-4

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152194 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000145

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461734 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727158

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

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

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111950

Other (OTH) AF: 0.0000166 AC: 1 AN: 60390

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152194 Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3 AN XY: 74352

African (AFR) AF: 0.000145 AC: 6 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.91
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.51	N
REVEL	Benign	0.056
Sift	Benign	0.085	T
Sift4G	Benign	0.30	T
Polyphen		0.13	B
Vest4		0.073
MutPred		0.23		Loss of sheet (P = 0.0142)
MVP		0.13
MPC		0.29
ClinPred		0.087	T
GERP RS		4.0
Varity_R		0.053
gMVP		0.23
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs367576965; hg19: chr17-4875562;