rs6135309

Variant names:

• chr20-14921876-T-C
• rs6135309
• NM_001351661.2:c.418+236917T>C

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+236917T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,158 control chromosomes in the GnomAD database, including 6,143 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 0.27 (6143 hom., cov: 33)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 11 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.418+236917T>C		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+236917T>C		intron_variant	Intron 5 of 17		NM_001351661.2	ENSP00000507484.1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40949 AN: 152038 Hom.: 6139 Cov.: 33

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.269 AC: 40962 AN: 152158 Hom.: 6143 Cov.: 33 AF XY: 0.275 AC XY: 20477 AN XY: 74386

African (AFR) AF: 0.147 AC: 6100 AN: 41542

American (AMR) AF: 0.335 AC: 5113 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 987 AN: 3468

East Asian (EAS) AF: 0.410 AC: 2120 AN: 5166

South Asian (SAS) AF: 0.511 AC: 2467 AN: 4826

European-Finnish (FIN) AF: 0.272 AC: 2878 AN: 10594

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20389 AN: 67980

Other (OTH) AF: 0.287 AC: 605 AN: 2106

Alfa AF: 0.287 Hom.: 8650

Bravo AF: 0.263

Asia WGS AF: 0.415 AC: 1440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.29
DANN	Benign	0.72
PhyloP100		-1.2
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: rs6135309; hg19: chr20-14902522;