rs2023385

Variant names:

• chr20-15670388-G-A
• rs2023385
• NM_001351661.2:c.645+170541G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.645+170541G>A		intron_variant	Intron 8 of 17	ENST00000684519.1	NP_001338590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.645+170541G>A		intron_variant	Intron 8 of 17		NM_001351661.2	ENSP00000507484.1
MACROD2	ENST00000402914.5	c.-61+170541G>A		intron_variant	Intron 4 of 13	1		ENSP00000385290.1
MACROD2	ENST00000642719.1	c.645+170541G>A		intron_variant	Intron 8 of 17			ENSP00000496601.1
MACROD2	ENST00000217246.8	c.645+170541G>A		intron_variant	Intron 8 of 16	2		ENSP00000217246.4

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

African (AFR) AF: 0.589 AC: 24399 AN: 41400

American (AMR) AF: 0.204 AC: 3119 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 352 AN: 3466

East Asian (EAS) AF: 0.166 AC: 856 AN: 5154

South Asian (SAS) AF: 0.230 AC: 1105 AN: 4814

European-Finnish (FIN) AF: 0.0418 AC: 442 AN: 10584

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.0459 AC: 3122 AN: 67998

Other (OTH) AF: 0.193 AC: 408 AN: 2112

Alfa AF: 0.145 Hom.: 1547

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
PhyloP100		-0.081
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

Other links and lift over

dbSNP: rs2023385; hg19: chr20-15651033;