12-22494922-G-T

Variant names:

• chr12-22494922-G-T
• rs10505879
• NM_001286176.2:c.1148-1585C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286176.2(C2CD5):​c.1148-1585C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 151,720 control chromosomes in the GnomAD database, including 31,966 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.60 (31966 hom., cov: 31)
• Consequence: C2CD5 NM_001286176.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C2CD5	NM_001286176.2	c.1148-1585C>A		intron_variant	Intron 10 of 26	ENST00000446597.6	NP_001273105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2CD5	ENST00000446597.6	c.1148-1585C>A		intron_variant	Intron 10 of 26	1	NM_001286176.2	ENSP00000388756.1

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91156 AN: 151602 Hom.: 31958 Cov.: 31

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.875

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.0528

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.648

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.601 AC: 91176 AN: 151720 Hom.: 31966 Cov.: 31 AF XY: 0.595 AC XY: 44117 AN XY: 74152

African (AFR) AF: 0.282 AC: 11655 AN: 41370

American (AMR) AF: 0.635 AC: 9662 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 2624 AN: 3464

East Asian (EAS) AF: 0.0531 AC: 274 AN: 5160

South Asian (SAS) AF: 0.587 AC: 2828 AN: 4814

European-Finnish (FIN) AF: 0.744 AC: 7841 AN: 10542

Middle Eastern (MID) AF: 0.728 AC: 211 AN: 290

European-Non Finnish (NFE) AF: 0.795 AC: 53926 AN: 67838

Other (OTH) AF: 0.644 AC: 1357 AN: 2108

Alfa AF: 0.739 Hom.: 114539

Bravo AF: 0.577

Asia WGS AF: 0.330 AC: 1139 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.36
DANN	Benign	0.46
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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: rs10505879; hg19: chr12-22647856;