20-14796294-A-G

Variant names:

• chr20-14796294-A-G
• rs980319
• NM_001351661.2:c.418+111335A>G

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+111335A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,888 control chromosomes in the GnomAD database, including 13,017 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 0.38 (13017 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.625
• Publications: 3 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=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.503 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+111335A>G		intron	N/A	NP_001338590.1	A1Z1Q3-1
	MACROD2	NM_001351663.2		c.418+111335A>G		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.418+111335A>G		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+111335A>G		intron	N/A	ENSP00000507484.1	A1Z1Q3-1
	MACROD2	ENST00000464883.5	TSL:1	n.182-96409A>G		intron	N/A
	MACROD2	ENST00000642719.1		c.418+111335A>G		intron	N/A	ENSP00000496601.1	A0A2R8YFN3

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57563 AN: 151770 Hom.: 13019 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.379 AC: 57541 AN: 151888 Hom.: 13017 Cov.: 32 AF XY: 0.378 AC XY: 28023 AN XY: 74190

African (AFR) AF: 0.159 AC: 6594 AN: 41428

American (AMR) AF: 0.339 AC: 5160 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 1571 AN: 3466

East Asian (EAS) AF: 0.158 AC: 813 AN: 5158

South Asian (SAS) AF: 0.321 AC: 1548 AN: 4816

European-Finnish (FIN) AF: 0.571 AC: 6020 AN: 10540

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.508 AC: 34484 AN: 67924

Other (OTH) AF: 0.396 AC: 835 AN: 2110

Alfa AF: 0.440 Hom.: 20099

Bravo AF: 0.350

Asia WGS AF: 0.228 AC: 796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	17
DANN	Benign	0.53
PhyloP100		0.63
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs980319; hg19: chr20-14776940;