NM_001351661.2:c.419-85653G>C

Variant names:

• chr20-15144287-G-C
• rs445251
• NM_001351661.2:c.419-85653G>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.419-85653G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 151,906 control chromosomes in the GnomAD database, including 26,556 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 0.59 (26556 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153
• Publications: 16 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 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.419-85653G>C		intron	N/A	NP_001338590.1
	MACROD2	NM_001351663.2		c.419-85653G>C		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.419-85653G>C		intron	N/A	NP_542407.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD2	ENST00000684519.1	MANE Select	c.419-85653G>C		intron	N/A	ENSP00000507484.1
	MACROD2	ENST00000642719.1		c.419-85653G>C		intron	N/A	ENSP00000496601.1
	MACROD2	ENST00000217246.8	TSL:2	c.419-85653G>C		intron	N/A	ENSP00000217246.4

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89510 AN: 151788 Hom.: 26526 Cov.: 32

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.590 AC: 89592 AN: 151906 Hom.: 26556 Cov.: 32 AF XY: 0.589 AC XY: 43692 AN XY: 74206

African (AFR) AF: 0.582 AC: 24086 AN: 41398

American (AMR) AF: 0.576 AC: 8800 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1939 AN: 3458

East Asian (EAS) AF: 0.650 AC: 3359 AN: 5168

South Asian (SAS) AF: 0.517 AC: 2491 AN: 4814

European-Finnish (FIN) AF: 0.617 AC: 6491 AN: 10518

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.597 AC: 40604 AN: 67974

Other (OTH) AF: 0.584 AC: 1229 AN: 2104

Alfa AF: 0.459 Hom.: 1214

Bravo AF: 0.591

Asia WGS AF: 0.551 AC: 1914 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.0
DANN	Benign	0.49
PhyloP100		0.15
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: rs445251; hg19: chr20-15124933;