NM_001286176.2:c.2368A>G

Variant names:

• chr12-22470902-T-C
• rs938801282
• NM_001286176.2:c.2368A>G

Variant summary

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

The NM_001286176.2(C2CD5):​c.2368A>G​(p.Thr790Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,609,228 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: C2CD5 NM_001286176.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.47
• Publications: 0 publications found

Genes affected

C2CD5 (HGNC:29062): (C2 calcium dependent domain containing 5) Enables calcium ion binding activity and calcium-dependent phospholipid binding activity. Involved in cellular response to insulin stimulus; intracellular protein transmembrane transport; and positive regulation of transport. Located in several cellular components, including centriolar satellite; cytoplasmic vesicle membrane; and ruffle membrane. [provided by Alliance of Genome Resources, Apr 2022]

C2CD5-AS1 (HGNC:55961): (C2CD5 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286176.2. 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
	C2CD5	NM_001286176.2	MANE Select	c.2368A>G	p.Thr790Ala	missense	Exon 21 of 27	NP_001273105.1	Q86YS7-3
	C2CD5	NM_001385322.1		c.2560A>G	p.Thr854Ala	missense	Exon 22 of 28	NP_001372251.1
	C2CD5	NM_001385323.1		c.2407A>G	p.Thr803Ala	missense	Exon 22 of 28	NP_001372252.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2CD5	ENST00000446597.6	TSL:1 MANE Select	c.2368A>G	p.Thr790Ala	missense	Exon 21 of 27	ENSP00000388756.1	Q86YS7-3
	C2CD5	ENST00000536386.5	TSL:1	c.2374A>G	p.Thr792Ala	missense	Exon 22 of 28	ENSP00000439392.1	Q86YS7-4
	C2CD5	ENST00000396028.6	TSL:1	c.2341A>G	p.Thr781Ala	missense	Exon 21 of 27	ENSP00000379345.2	Q86YS7-2

Frequencies

GnomAD3 genomes AF: 0.0000658 AC: 10 AN: 152044 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

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

GnomAD2 exomes AF: 0.0000242 AC: 6 AN: 247566 AF XY: 0.0000224

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000178

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000755 AC: 11 AN: 1457184 Hom.: 0 Cov.: 28 AF XY: 0.00000689 AC XY: 5 AN XY: 725170

African (AFR) AF: 0.00 AC: 0 AN: 33330

American (AMR) AF: 0.000135 AC: 6 AN: 44560

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39612

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1108290

Other (OTH) AF: 0.0000332 AC: 2 AN: 60216

GnomAD4 genome AF: 0.0000658 AC: 10 AN: 152044 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74252

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.000590 AC: 9 AN: 15254

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: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67920

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000132

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Uncertain	0.12
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.29	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		6.5
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.43
Sift	Benign	0.051	T
Sift4G	Benign	0.089	T
Polyphen		0.47	P
Vest4		0.78
MutPred		0.42		Gain of catalytic residue at A793 (P = 0.0017)
MVP		0.76
MPC		0.50
ClinPred		0.62	D
GERP RS		5.0
Varity_R		0.27
gMVP		0.69
Mutation Taster		=65/35	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: rs938801282; hg19: chr12-22623836;