21-41905765-C-G

Variant names:

• chr21-41905765-C-G
• NM_015500.2:c.1391G>C

Variant summary

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

The NM_015500.2(C2CD2):​c.1391G>C​(p.Arg464Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: C2CD2 NM_015500.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.579

Genes affected

C2CD2 (HGNC:1266): (C2 calcium dependent domain containing 2) Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.099554926).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C2CD2	NM_015500.2	c.1391G>C	p.Arg464Pro	missense_variant	Exon 11 of 14	ENST00000380486.4	NP_056315.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2CD2	ENST00000380486.4	c.1391G>C	p.Arg464Pro	missense_variant	Exon 11 of 14	1	NM_015500.2	ENSP00000369853.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458766 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 725826

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	14
DANN	Benign	0.88
DEOGEN2	Benign	0.069	.;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.90	T
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.14
Sift	Benign	0.26	T;T
Sift4G	Benign	0.26	T;T
Polyphen		0.88	.;P
Vest4		0.23
MutPred		0.30		.;Gain of sheet (P = 0.0221);
MVP		0.72
MPC		0.37
ClinPred		0.42	T
GERP RS		1.8
Varity_R		0.28
gMVP		0.26

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: chr21-43325874;