chr20-14014568-T-G

Variant names:

• chr20-14014568-T-G
• rs10485770
• NM_001351661.2:c.163+12164T>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.163+12164T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,090 control chromosomes in the GnomAD database, including 1,939 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 0.15 (1939 hom., cov: 31)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.21 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.163+12164T>G		intron	N/A	NP_001338590.1	A1Z1Q3-1
	MACROD2	NM_001351663.2		c.163+12164T>G		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.163+12164T>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.163+12164T>G		intron	N/A	ENSP00000507484.1	A1Z1Q3-1
	MACROD2	ENST00000483997.5	TSL:1	n.425+12164T>G		intron	N/A
	MACROD2	ENST00000642719.1		c.163+12164T>G		intron	N/A	ENSP00000496601.1	A0A2R8YFN3

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23044 AN: 151970 Hom.: 1939 Cov.: 31

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.152 AC: 23056 AN: 152090 Hom.: 1939 Cov.: 31 AF XY: 0.154 AC XY: 11453 AN XY: 74348

African (AFR) AF: 0.104 AC: 4301 AN: 41514

American (AMR) AF: 0.216 AC: 3297 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 708 AN: 3468

East Asian (EAS) AF: 0.205 AC: 1057 AN: 5158

South Asian (SAS) AF: 0.209 AC: 1008 AN: 4820

European-Finnish (FIN) AF: 0.174 AC: 1841 AN: 10558

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10243 AN: 67986

Other (OTH) AF: 0.160 AC: 338 AN: 2112

Alfa AF: 0.0723 Hom.: 80

Bravo AF: 0.152

Asia WGS AF: 0.188 AC: 651 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.4
DANN	Benign	0.48
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10485770; hg19: chr20-13995214;