12-22470874-T-C

Variant names:

• chr12-22470874-T-C
• NM_001286176.2:c.2396A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001286176.2(C2CD5):​c.2396A>G​(p.Asn799Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: C2CD5 NM_001286176.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.47

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19796675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C2CD5	NM_001286176.2	c.2396A>G	p.Asn799Ser	missense_variant	Exon 21 of 27	ENST00000446597.6	NP_001273105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2CD5	ENST00000446597.6	c.2396A>G	p.Asn799Ser	missense_variant	Exon 21 of 27	1	NM_001286176.2	ENSP00000388756.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460558 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726628

Gnomad4 AFR exome AF: 0.00

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.028	T;.;.;.;.;.
Eigen	Benign	-0.17
Eigen_PC	Benign	0.049
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;.;D;D;D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.20	T;T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.69	N;N;.;.;N;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.76	N;N;N;N;N;N
REVEL	Benign	0.074
Sift	Benign	0.24	T;T;T;T;T;T
Sift4G	Benign	0.62	T;T;T;T;T;T
Polyphen		0.0010	B;.;.;B;.;.
Vest4		0.41
MutPred		0.17		Gain of disorder (P = 0.0697);Gain of disorder (P = 0.0697);.;.;Gain of disorder (P = 0.0697);.;
MVP		0.53
MPC		0.32
ClinPred		0.80	D
GERP RS		5.0
Varity_R		0.085
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-22623808;