rs6135562

Positions:

• chr20-15826796-T-C

Variant summary

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

The NM_001351661.2(MACROD2):​c.646-35949T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,220 control chromosomes in the GnomAD database, including 2,060 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 0.14 (2060 hom., cov: 33)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570

Genes affected

MACROD2 (HGNC:16126): (mono-ADP ribosylhydrolase 2) The protein encoded by this gene is a deacetylase involved in removing ADP-ribose from mono-ADP-ribosylated proteins. The encoded protein has been shown to translocate from the nucleus to the cytoplasm upon DNA damage. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACROD2	NM_001351661.2	c.646-35949T>C		intron_variant		ENST00000684519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACROD2	ENST00000684519.1	c.646-35949T>C		intron_variant			NM_001351661.2	P2
MACROD2	ENST00000402914.5	c.-60-35949T>C		intron_variant		1
MACROD2	ENST00000217246.8	c.646-35949T>C		intron_variant		2		A2
MACROD2	ENST00000642719.1	c.646-35949T>C		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21570 AN: 152102 Hom.: 2052 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0610

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.0923

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.142 AC: 21604 AN: 152220 Hom.: 2060 Cov.: 33 AF XY: 0.145 AC XY: 10780 AN XY: 74438

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.0610

Gnomad4 NFE AF: 0.0923

Gnomad4 OTH AF: 0.169

Alfa AF: 0.114 Hom.: 1664

Bravo AF: 0.159

Asia WGS AF: 0.273 AC: 943 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.3
DANN	Benign	0.54

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: rs6135562; hg19: chr20-15807441;