11-119110553-G-A

Position:

• chr11-119110553-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001290474.2(C2CD2L):​c.451-8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,605,886 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0059 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00062 (13 hom.)
• Consequence: C2CD2L NM_001290474.2 splice_region, intron
• Scores: Splicing: ADA: 0.9885
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0840

Genes affected

C2CD2L (HGNC:29000): (C2CD2 like) Enables phosphatidylinositol binding activity and phosphatidylinositol transfer activity. Involved in positive regulation of insulin secretion involved in cellular response to glucose stimulus. Located in cortical endoplasmic reticulum and endoplasmic reticulum-plasma membrane contact site. Colocalizes with cytoplasmic side of apical plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 11-119110553-G-A is Benign according to our data. Variant chr11-119110553-G-A is described in ClinVar as [Benign]. Clinvar id is 776665.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0059 (898/152236) while in subpopulation AFR AF= 0.0198 (823/41522). AF 95% confidence interval is 0.0187. There are 5 homozygotes in gnomad4. There are 428 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 898 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2CD2L	NM_001290474.2	c.451-8G>A		splice_region_variant, intron_variant		ENST00000648610.2	NP_001277403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C2CD2L	ENST00000648610.2	c.451-8G>A		splice_region_variant, intron_variant			NM_001290474.2	ENSP00000497391.1
C2CD2L	ENST00000336702.7	c.451-8G>A		splice_region_variant, intron_variant		1		ENSP00000338885.3
C2CD2L	ENST00000529874.5	n.98-8G>A		splice_region_variant, intron_variant		3
C2CD2L	ENST00000525598.1	n.-34G>A		upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.00590 AC: 897 AN: 152118 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.0199

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00164 AC: 397 AN: 242006 Hom.: 4 AF XY: 0.00111 AC XY: 145 AN XY: 131166

Gnomad AFR exome AF: 0.0218

Gnomad AMR exome AF: 0.00114

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000167

Gnomad SAS exome AF: 0.0000335

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000455

Gnomad OTH exome AF: 0.00168

GnomAD4 exome AF: 0.000623 AC: 905 AN: 1453650 Hom.: 13 Cov.: 32 AF XY: 0.000537 AC XY: 388 AN XY: 723094

Gnomad4 AFR exome AF: 0.0217

Gnomad4 AMR exome AF: 0.00149

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000506

Gnomad4 SAS exome AF: 0.0000701

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000171

Gnomad4 OTH exome AF: 0.00145

GnomAD4 genome AF: 0.00590 AC: 898 AN: 152236 Hom.: 5 Cov.: 33 AF XY: 0.00575 AC XY: 428 AN XY: 74438

Gnomad4 AFR AF: 0.0198

Gnomad4 AMR AF: 0.00373

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.00102 Hom.: 0

Bravo AF: 0.00674

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	20
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Benign	0.63
SpliceAI score (max)		0.99		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.99		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs77672284; hg19: chr11-118981263;