rs6135305

Variant names:

• chr20-14909565-G-A
• rs6135305
• NM_001351661.2:c.418+224606G>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+224606G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 151,566 control chromosomes in the GnomAD database, including 1,690 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 0.14 (1690 hom., cov: 31)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.418+224606G>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+224606G>A		intron_variant	Intron 5 of 17		NM_001351661.2	ENSP00000507484.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21734 AN: 151446 Hom.: 1684 Cov.: 31

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.144 AC: 21763 AN: 151566 Hom.: 1690 Cov.: 31 AF XY: 0.143 AC XY: 10611 AN XY: 74058

African (AFR) AF: 0.150 AC: 6196 AN: 41300

American (AMR) AF: 0.171 AC: 2604 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 741 AN: 3456

East Asian (EAS) AF: 0.233 AC: 1187 AN: 5100

South Asian (SAS) AF: 0.108 AC: 517 AN: 4788

European-Finnish (FIN) AF: 0.118 AC: 1237 AN: 10500

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.129 AC: 8738 AN: 67914

Other (OTH) AF: 0.164 AC: 344 AN: 2098

Alfa AF: 0.139 Hom.: 5022

Bravo AF: 0.151

Asia WGS AF: 0.156 AC: 545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.39
PhyloP100		-0.052
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: rs6135305; hg19: chr20-14890211;