rs6135125

Variant names:

• chr20-14345094-A-G
• rs6135125
• NM_001351661.2:c.272-148385A>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.272-148385A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,222 control chromosomes in the GnomAD database, including 2,609 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 0.16 (2609 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.923
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.272-148385A>G		intron_variant	Intron 3 of 17	ENST00000684519.1	NP_001338590.1
MACROD2	NM_001351663.2	c.272-148385A>G		intron_variant	Intron 3 of 17		NP_001338592.1
MACROD2	NM_080676.6	c.272-148385A>G		intron_variant	Intron 3 of 16		NP_542407.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.272-148385A>G		intron_variant	Intron 3 of 17		NM_001351661.2	ENSP00000507484.1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24950 AN: 152102 Hom.: 2609 Cov.: 32

Gnomad AFR AF: 0.0412

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.164 AC: 24949 AN: 152222 Hom.: 2609 Cov.: 32 AF XY: 0.168 AC XY: 12490 AN XY: 74424

African (AFR) AF: 0.0411 AC: 1709 AN: 41538

American (AMR) AF: 0.154 AC: 2350 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 662 AN: 3472

East Asian (EAS) AF: 0.306 AC: 1585 AN: 5178

South Asian (SAS) AF: 0.272 AC: 1313 AN: 4828

European-Finnish (FIN) AF: 0.247 AC: 2616 AN: 10588

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14043 AN: 68012

Other (OTH) AF: 0.181 AC: 383 AN: 2112

Alfa AF: 0.169 Hom.: 417

Bravo AF: 0.150

Asia WGS AF: 0.292 AC: 1014 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.78
PhyloP100		0.92
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: rs6135125; hg19: chr20-14325740;