rs1591985831

Variant names:

• chr12-22472010-G-C
• rs1591985831
• NM_001286176.2:c.2225C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001286176.2(C2CD5):​c.2225C>G​(p.Ala742Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,457,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: C2CD5 NM_001286176.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.33
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17923597).

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.2225C>G	p.Ala742Gly	missense	Exon 19 of 27	NP_001273105.1	Q86YS7-3
	C2CD5	NM_001385322.1		c.2417C>G	p.Ala806Gly	missense	Exon 20 of 28	NP_001372251.1
	C2CD5	NM_001385323.1		c.2264C>G	p.Ala755Gly	missense	Exon 20 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.2225C>G	p.Ala742Gly	missense	Exon 19 of 27	ENSP00000388756.1	Q86YS7-3
	C2CD5	ENST00000536386.5	TSL:1	c.2231C>G	p.Ala744Gly	missense	Exon 20 of 28	ENSP00000439392.1	Q86YS7-4
	C2CD5	ENST00000396028.6	TSL:1	c.2198C>G	p.Ala733Gly	missense	Exon 19 of 27	ENSP00000379345.2	Q86YS7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1457622 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 725252

African (AFR) AF: 0.00 AC: 0 AN: 33328

American (AMR) AF: 0.00 AC: 0 AN: 44542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26032

East Asian (EAS) AF: 0.00 AC: 0 AN: 39510

South Asian (SAS) AF: 0.00 AC: 0 AN: 86024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1108886

Other (OTH) AF: 0.00 AC: 0 AN: 60194

GnomAD4 genome Cov.: 32

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	0.086
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.55	N
PhyloP100		4.3
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.097
Sift	Benign	0.23	T
Sift4G	Benign	0.45	T
Polyphen		0.0	B
Vest4		0.082
MutPred		0.29		Loss of helix (P = 0.0444)
MVP		0.75
MPC		0.40
ClinPred		0.52	D
GERP RS		5.7
PromoterAI		-0.0034	Neutral
Varity_R		0.099
gMVP		0.29
Mutation Taster		=89/11	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: rs1591985831; hg19: chr12-22624944;