20-14884510-T-C

Variant names:

• chr20-14884510-T-C
• rs14135
• NM_001351661.2:c.418+199551T>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+199551T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,046 control chromosomes in the GnomAD database, including 5,286 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 0.25 (5282 hom., cov: 32)
  • Exomes 𝑓: 0.37 (4 hom.)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.355 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.418+199551T>C		intron	N/A	NP_001338590.1	A1Z1Q3-1
	MACROD2	NM_001351663.2		c.418+199551T>C		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.418+199551T>C		intron	N/A	NP_542407.2	A1Z1Q3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD2	ENST00000684519.1	MANE Select	c.418+199551T>C		intron	N/A	ENSP00000507484.1	A1Z1Q3-1
	MACROD2	ENST00000464883.5	TSL:1	n.182-8193T>C		intron	N/A
	MACROD2	ENST00000642719.1		c.418+199551T>C		intron	N/A	ENSP00000496601.1	A0A2R8YFN3

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38160 AN: 151872 Hom.: 5277 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.232

GnomAD4 exome AF: 0.370 AC: 20 AN: 54 Hom.: 4 Cov.: 0 AF XY: 0.333 AC XY: 16 AN XY: 48

African (AFR) AF: 0.500 AC: 2 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.386 AC: 17 AN: 44

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.251 AC: 38174 AN: 151992 Hom.: 5282 Cov.: 32 AF XY: 0.249 AC XY: 18473 AN XY: 74270

African (AFR) AF: 0.360 AC: 14935 AN: 41452

American (AMR) AF: 0.192 AC: 2928 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 513 AN: 3472

East Asian (EAS) AF: 0.149 AC: 770 AN: 5160

South Asian (SAS) AF: 0.145 AC: 695 AN: 4800

European-Finnish (FIN) AF: 0.278 AC: 2933 AN: 10556

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14704 AN: 67962

Other (OTH) AF: 0.228 AC: 481 AN: 2106

Alfa AF: 0.224 Hom.: 15470

Bravo AF: 0.249

Asia WGS AF: 0.159 AC: 553 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.7
DANN	Benign	0.64
PhyloP100		-0.021
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: rs14135; hg19: chr20-14865156;