rs746631048

Variant names:

• chr21-41889212-G-A
• rs746631048
• NM_015500.2:c.2003C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-41889212-G-A
• chr21-41889212-G-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.2003C>T​(p.Thr668Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,362 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: C2CD2 NM_015500.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.28

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=0.24313039).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C2CD2	NM_015500.2	c.2003C>T	p.Thr668Ile	missense_variant	Exon 14 of 14	ENST00000380486.4	NP_056315.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2CD2	ENST00000380486.4	c.2003C>T	p.Thr668Ile	missense_variant	Exon 14 of 14	1	NM_015500.2	ENSP00000369853.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251320 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135894

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461362 Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6 AN XY: 726976

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: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	.;T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.11
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.95	T
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.8	D;D
REVEL	Benign	0.15
Sift	Benign	0.039	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.25	.;B
Vest4		0.39
MutPred		0.25		.;Loss of phosphorylation at T668 (P = 0.0424);
MVP		0.52
MPC		0.36
ClinPred		0.47	T
GERP RS		3.3
Varity_R		0.21
gMVP		0.39

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

LitVar

Other links and lift over

dbSNP: rs746631048; hg19: chr21-43309321;