rs451390

Positions:

• chr21-41923401-G-C

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C2CD2	NM_015500.2	c.379-1316C>G		intron_variant		ENST00000380486.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C2CD2	ENST00000380486.4	c.379-1316C>G		intron_variant		1	NM_015500.2	P1
C2CD2	ENST00000329623.11	c.-87-1316C>G		intron_variant		1
C2CD2	ENST00000467074.6	n.102-1316C>G		intron_variant, non_coding_transcript_variant		5
C2CD2	ENST00000490479.1	n.15-1316C>G		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.0358

Gnomad4 ASJ AF: 0.0256

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0740

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.00738

Gnomad4 OTH AF: 0.0536

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs451390; hg19: chr21-43343510;