rs451390

Variant names:

• chr21-41923401-G-C
• rs451390
• NM_015500.2:c.379-1316C>G

Variant summary

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

The NM_015500.2(C2CD2):​c.379-1316C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0722 in 152,172 control chromosomes in the GnomAD database, including 1,137 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 0.072 (1137 hom., cov: 32)
• Consequence: C2CD2 NM_015500.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

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.379-1316C>G		intron	N/A	NP_056315.1	Q9Y426-1
	C2CD2	NM_199050.3		c.-87-1316C>G		intron	N/A	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.379-1316C>G		intron	N/A	ENSP00000369853.3	Q9Y426-1
	C2CD2	ENST00000329623.11	TSL:1	c.-87-1316C>G		intron	N/A	ENSP00000329302.7	Q9Y426-2
	C2CD2	ENST00000890791.1		c.379-1316C>G		intron	N/A	ENSP00000560850.1

Frequencies

GnomAD3 genomes AF: 0.0721 AC: 10967 AN: 152054 Hom.: 1138 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0359

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0735

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00737

Gnomad OTH AF: 0.0541

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

GnomAD4 genome AF: 0.0722 AC: 10985 AN: 152172 Hom.: 1137 Cov.: 32 AF XY: 0.0711 AC XY: 5287 AN XY: 74410

African (AFR) AF: 0.226 AC: 9363 AN: 41504

American (AMR) AF: 0.0358 AC: 547 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0256 AC: 89 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0740 AC: 357 AN: 4824

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10598

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00738 AC: 502 AN: 68000

Other (OTH) AF: 0.0536 AC: 113 AN: 2110

Alfa AF: 0.0449 Hom.: 91

Bravo AF: 0.0813

Asia WGS AF: 0.0430 AC: 152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.42
PhyloP100		-0.30
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: rs451390; hg19: chr21-43343510;