rs2023385

Positions:

• chr20-15670388-G-A

Variant summary

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

The NM_001351661.2(MACROD2):​c.645+170541G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,004 control chromosomes in the GnomAD database, including 8,024 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 0.22 (8024 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACROD2	NM_001351661.2	c.645+170541G>A		intron_variant		ENST00000684519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACROD2	ENST00000684519.1	c.645+170541G>A		intron_variant			NM_001351661.2	P2
MACROD2	ENST00000402914.5	c.-61+170541G>A		intron_variant		1
MACROD2	ENST00000217246.8	c.645+170541G>A		intron_variant		2		A2
MACROD2	ENST00000642719.1	c.645+170541G>A		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33791 AN: 151886 Hom.: 8003 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.0418

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.0459

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.223 AC: 33871 AN: 152004 Hom.: 8024 Cov.: 32 AF XY: 0.222 AC XY: 16487 AN XY: 74314

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.0418

Gnomad4 NFE AF: 0.0459

Gnomad4 OTH AF: 0.193

Alfa AF: 0.135 Hom.: 1144

Bravo AF: 0.251

Asia WGS AF: 0.253 AC: 880 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	2.2
DANN	Benign	0.53

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: rs2023385; hg19: chr20-15651033;