rs6085020

Variant names:

• chr20-5167951-T-C
• rs6085020
• NM_003818.4:c.58-5572T>C

Variant summary

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

The NM_003818.4(CDS2):​c.58-5572T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 152,074 control chromosomes in the GnomAD database, including 15,280 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 0.44 (15280 hom., cov: 32)
• Consequence: CDS2 NM_003818.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.72

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDS2	NM_003818.4	c.58-5572T>C		intron_variant	Intron 1 of 12	ENST00000460006.6	NP_003809.1
CDS2	XM_006723660.3	c.58-5572T>C		intron_variant	Intron 1 of 11		XP_006723723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDS2	ENST00000460006.6	c.58-5572T>C		intron_variant	Intron 1 of 12	1	NM_003818.4	ENSP00000419879.1

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67443 AN: 151956 Hom.: 15264 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.444 AC: 67493 AN: 152074 Hom.: 15280 Cov.: 32 AF XY: 0.439 AC XY: 32655 AN XY: 74340

Gnomad4 AFR AF: 0.445 AC: 0.445141 AN: 0.445141

Gnomad4 AMR AF: 0.374 AC: 0.374427 AN: 0.374427

Gnomad4 ASJ AF: 0.549 AC: 0.548731 AN: 0.548731

Gnomad4 EAS AF: 0.260 AC: 0.259645 AN: 0.259645

Gnomad4 SAS AF: 0.597 AC: 0.596928 AN: 0.596928

Gnomad4 FIN AF: 0.383 AC: 0.38327 AN: 0.38327

Gnomad4 NFE AF: 0.467 AC: 0.466787 AN: 0.466787

Gnomad4 OTH AF: 0.440 AC: 0.440397 AN: 0.440397

Alfa AF: 0.441 Hom.: 2234

Bravo AF: 0.437

Asia WGS AF: 0.402 AC: 1400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.049
DANN	Benign	0.62
Mutation Taster		=100/0	polymorphism (auto)

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: rs6085020; hg19: chr20-5148597;