chr21-41905834-G-C

Variant names:

• chr21-41905834-G-C
• rs1244388047
• NM_015500.2:c.1322C>G

Variant summary

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

The NM_015500.2(C2CD2):​c.1322C>G​(p.Ser441Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: C2CD2 NM_015500.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.64
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015500.2. 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
	C2CD2	NM_015500.2	MANE Select	c.1322C>G	p.Ser441Cys	missense	Exon 11 of 14	NP_056315.1	Q9Y426-1
	C2CD2	NM_199050.3		c.857C>G	p.Ser286Cys	missense	Exon 10 of 13	NP_950251.1	Q9Y426-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2CD2	ENST00000380486.4	TSL:1 MANE Select	c.1322C>G	p.Ser441Cys	missense	Exon 11 of 14	ENSP00000369853.3	Q9Y426-1
	C2CD2	ENST00000329623.11	TSL:1	c.857C>G	p.Ser286Cys	missense	Exon 10 of 13	ENSP00000329302.7	Q9Y426-2
	C2CD2	ENST00000482186.5	TSL:1	n.1322C>G		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251272 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000144 AC: 2 AN: 1390712 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 695880

African (AFR) AF: 0.00 AC: 0 AN: 32088

American (AMR) AF: 0.0000448 AC: 2 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25728

East Asian (EAS) AF: 0.00 AC: 0 AN: 39312

South Asian (SAS) AF: 0.00 AC: 0 AN: 84860

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5622

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1047224

Other (OTH) AF: 0.00 AC: 0 AN: 57892

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.14
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Benign	0.92
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.87	T
PhyloP100		6.6
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.20
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.082	T
Polyphen		0.15	B
Vest4		0.50
MutPred		0.16		Loss of phosphorylation at S441 (P = 0.029)
MVP		0.49
MPC		0.88
ClinPred		0.88	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.45
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs1244388047; hg19: chr21-43325943;