rs2420

Variant names:

• chr1-167917264-A-T
• rs2420
• NM_001143674.4:c.*1059T>A

Variant summary

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

The NM_001143674.4(MPC2):​c.*1059T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,090 control chromosomes in the GnomAD database, including 3,827 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 0.20 (3827 hom., cov: 32)
  • Exomes 𝑓: 0.33 (0 hom.)
• Consequence: MPC2 NM_001143674.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.288

Genes affected

MPC2 (HGNC:24515): (mitochondrial pyruvate carrier 2) Enables identical protein binding activity. Predicted to be involved in mitochondrial pyruvate transmembrane transport. Predicted to act upstream of or within mitochondrial acetyl-CoA biosynthetic process from pyruvate and positive regulation of insulin secretion involved in cellular response to glucose stimulus. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

DCAF6 (HGNC:30002): (DDB1 and CUL4 associated factor 6) The protein encoded by this gene is a ligand-dependent coactivator of nuclear receptors, including nuclear receptor subfamily 3 group C member 1 (NR3C1), glucocorticoid receptor (GR), and androgen receptor (AR). The encoded protein and DNA damage binding protein 2 (DDB2) may act as tumor promoters and tumor suppressors, respectively, by regulating the level of androgen receptor in prostate tissues. In addition, this protein can act with glucocorticoid receptor to promote human papillomavirus gene expression. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPC2	NM_001143674.4	c.*1059T>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000271373.9	NP_001137146.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPC2	ENST00000271373	c.*1059T>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_001143674.4	ENSP00000271373.4
MPC2	ENST00000367846	c.*1059T>A		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000356820.4

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30827 AN: 151960 Hom.: 3824 Cov.: 32

Gnomad AFR AF: 0.0811

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.333 AC: 4 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.300 AC XY: 3 AN XY: 10

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.203 AC: 30839 AN: 152078 Hom.: 3827 Cov.: 32 AF XY: 0.204 AC XY: 15173 AN XY: 74306

Gnomad4 AFR AF: 0.0809

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.218

Alfa AF: 0.222 Hom.: 560

Bravo AF: 0.213

Asia WGS AF: 0.158 AC: 552 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.43

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: rs2420; hg19: chr1-167886502;