12-22470862-T-C

Variant names:

• chr12-22470862-T-C
• rs1465102562
• NM_001286176.2:c.2408A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001286176.2(C2CD5):​c.2408A>G​(p.Gln803Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. Q803P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: C2CD5 NM_001286176.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.87
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32677975).

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.2408A>G	p.Gln803Arg	missense	Exon 21 of 27	NP_001273105.1	Q86YS7-3
	C2CD5	NM_001385322.1		c.2600A>G	p.Gln867Arg	missense	Exon 22 of 28	NP_001372251.1
	C2CD5	NM_001385323.1		c.2447A>G	p.Gln816Arg	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.2408A>G	p.Gln803Arg	missense	Exon 21 of 27	ENSP00000388756.1	Q86YS7-3
	C2CD5	ENST00000536386.5	TSL:1	c.2414A>G	p.Gln805Arg	missense	Exon 22 of 28	ENSP00000439392.1	Q86YS7-4
	C2CD5	ENST00000396028.6	TSL:1	c.2381A>G	p.Gln794Arg	missense	Exon 21 of 27	ENSP00000379345.2	Q86YS7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460578 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726620

African (AFR) AF: 0.00 AC: 0 AN: 33426

American (AMR) AF: 0.00 AC: 0 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.00 AC: 0 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111082

Other (OTH) AF: 0.00 AC: 0 AN: 60320

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Benign	0.034
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.9
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.13
Sift	Benign	0.28	T
Sift4G	Benign	0.55	T
Polyphen		0.0070	B
Vest4		0.51
MutPred		0.25		Loss of ubiquitination at K806 (P = 0.0184)
MVP		0.70
MPC		0.46
ClinPred		0.66	D
GERP RS		5.0
Varity_R		0.21
gMVP		0.32
Mutation Taster		=91/9	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: rs1465102562; hg19: chr12-22623796;