20-14925213-G-A

Variant names:

• chr20-14925213-G-A
• rs1408428
• NM_001351661.2:c.418+240254G>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+240254G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,802 control chromosomes in the GnomAD database, including 25,346 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 0.57 (25346 hom., cov: 31)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.418+240254G>A		intron_variant	Intron 5 of 17	ENST00000684519.1	NP_001338590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.418+240254G>A		intron_variant	Intron 5 of 17		NM_001351661.2	ENSP00000507484.1

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87171 AN: 151684 Hom.: 25317 Cov.: 31

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.575 AC: 87256 AN: 151802 Hom.: 25346 Cov.: 31 AF XY: 0.574 AC XY: 42594 AN XY: 74180

African (AFR) AF: 0.606 AC: 25091 AN: 41406

American (AMR) AF: 0.591 AC: 9006 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1700 AN: 3468

East Asian (EAS) AF: 0.618 AC: 3174 AN: 5140

South Asian (SAS) AF: 0.727 AC: 3496 AN: 4806

European-Finnish (FIN) AF: 0.472 AC: 4964 AN: 10514

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.561 AC: 38093 AN: 67916

Other (OTH) AF: 0.549 AC: 1156 AN: 2106

Alfa AF: 0.573 Hom.: 11601

Bravo AF: 0.581

Asia WGS AF: 0.686 AC: 2384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.28
PhyloP100		0.23
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: rs1408428; hg19: chr20-14905859;