rs2295509

Positions:

• chr20-5182617-G-A
• chr20-5182617-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003818.4(CDS2):​c.588+172G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,154 control chromosomes in the GnomAD database, including 2,383 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 0.16 (2383 hom., cov: 32)
• Consequence: CDS2 NM_003818.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.762

Genes affected

CDS2 (HGNC:1801): (CDP-diacylglycerol synthase 2) Breakdown products of phosphoinositides are ubiquitous second messengers that function downstream of many G protein-coupled receptors and tyrosine kinases regulating cell growth, calcium metabolism, and protein kinase C activity. This gene encodes an enzyme which regulates the amount of phosphatidylinositol available for signaling by catalyzing the conversion of phosphatidic acid to CDP-diacylglycerol. This enzyme is an integral membrane protein localized to two subcellular domains, the matrix side of the inner mitochondrial membrane where it is thought to be involved in the synthesis of phosphatidylglycerol and cardiolipin and the cytoplasmic side of the endoplasmic reticulum where it functions in phosphatidylinositol biosynthesis. Two genes encoding this enzyme have been identified in humans, one mapping to human chromosome 4q21 and a second to 20p13. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDS2	NM_003818.4	c.588+172G>A		intron_variant		ENST00000460006.6	NP_003809.1
CDS2	XM_006723660.3	c.588+172G>A		intron_variant			XP_006723723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDS2	ENST00000460006.6	c.588+172G>A		intron_variant		1	NM_003818.4	ENSP00000419879	P1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24471 AN: 152036 Hom.: 2373 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.0661

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.161 AC: 24510 AN: 152154 Hom.: 2383 Cov.: 32 AF XY: 0.158 AC XY: 11770 AN XY: 74382

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.0661

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.160

Alfa AF: 0.0886 Hom.: 204

Bravo AF: 0.168

Asia WGS AF: 0.187 AC: 650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.20
DANN	Benign	0.33

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: rs2295509; hg19: chr20-5163263;