20-14234955-T-G

Variant names:

• chr20-14234955-T-G
• rs7268327
• NM_001351661.2:c.271+149227T>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001351661.2(MACROD2):​c.271+149227T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,134 control chromosomes in the GnomAD database, including 3,106 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 0.17 (3106 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD2	NM_001351661.2	MANE Select	c.271+149227T>G		intron	N/A	NP_001338590.1
	MACROD2	NM_001351663.2		c.271+149227T>G		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.271+149227T>G		intron	N/A	NP_542407.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD2	ENST00000684519.1	MANE Select	c.271+149227T>G		intron	N/A	ENSP00000507484.1
	MACROD2	ENST00000642719.1		c.271+149227T>G		intron	N/A	ENSP00000496601.1
	MACROD2	ENST00000217246.8	TSL:2	c.271+149227T>G		intron	N/A	ENSP00000217246.4

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25440 AN: 152016 Hom.: 3106 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0901

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0871

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.0828

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.167 AC: 25465 AN: 152134 Hom.: 3106 Cov.: 32 AF XY: 0.166 AC XY: 12317 AN XY: 74376

African (AFR) AF: 0.339 AC: 14061 AN: 41452

American (AMR) AF: 0.142 AC: 2166 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0901 AC: 313 AN: 3472

East Asian (EAS) AF: 0.245 AC: 1266 AN: 5166

South Asian (SAS) AF: 0.131 AC: 631 AN: 4832

European-Finnish (FIN) AF: 0.0871 AC: 923 AN: 10600

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.0828 AC: 5628 AN: 68002

Other (OTH) AF: 0.160 AC: 338 AN: 2110

Alfa AF: 0.0805 Hom.: 187

Bravo AF: 0.182

Asia WGS AF: 0.187 AC: 650 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.82
PhyloP100		2.1
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: rs7268327; hg19: chr20-14215601;