rs2423846

Variant names:

• chr20-14921130-G-A
• rs2423846
• NM_001351661.2:c.418+236171G>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.418+236171G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 152,002 control chromosomes in the GnomAD database, including 20,527 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 0.51 (20527 hom., cov: 33)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282
• Publications: 6 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]

MACROD2-AS1 (HGNC:37193): (MACROD2 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351661.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD2	NM_001351661.2	MANE Select	c.418+236171G>A		intron	N/A	NP_001338590.1	A1Z1Q3-1
	MACROD2	NM_001351663.2		c.418+236171G>A		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.418+236171G>A		intron	N/A	NP_542407.2	A1Z1Q3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD2	ENST00000684519.1	MANE Select	c.418+236171G>A		intron	N/A	ENSP00000507484.1	A1Z1Q3-1
	MACROD2-AS1	ENST00000439451.1	TSL:1	n.141+8245C>T		intron	N/A
	MACROD2	ENST00000642719.1		c.418+236171G>A		intron	N/A	ENSP00000496601.1	A0A2R8YFN3

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78105 AN: 151882 Hom.: 20504 Cov.: 33

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.514 AC: 78176 AN: 152002 Hom.: 20527 Cov.: 33 AF XY: 0.515 AC XY: 38255 AN XY: 74288

African (AFR) AF: 0.431 AC: 17849 AN: 41460

American (AMR) AF: 0.538 AC: 8210 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1659 AN: 3464

East Asian (EAS) AF: 0.581 AC: 2999 AN: 5160

South Asian (SAS) AF: 0.715 AC: 3447 AN: 4824

European-Finnish (FIN) AF: 0.469 AC: 4940 AN: 10538

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.551 AC: 37456 AN: 67974

Other (OTH) AF: 0.501 AC: 1058 AN: 2110

Alfa AF: 0.538 Hom.: 67002

Bravo AF: 0.510

Asia WGS AF: 0.644 AC: 2236 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.4
DANN	Benign	0.50
PhyloP100		0.28
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: rs2423846; hg19: chr20-14901776;