rs2549855

Variant names:

• chr16-80993247-C-G
• rs2549855
• NM_020188.5:c.81+4067G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020188.5(CMC2):​c.81+4067G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 152,008 control chromosomes in the GnomAD database, including 34,100 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 0.65 (34100 hom., cov: 32)
• Consequence: CMC2 NM_020188.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.727
• Publications: 9 publications found

Genes affected

CMC2 (HGNC:24447): (C-X9-C motif containing 2) Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286221 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMC2	NM_020188.5	c.81+4067G>C		intron_variant	Intron 2 of 3	ENST00000219400.8	NP_064573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CMC2	ENST00000219400.8	c.81+4067G>C		intron_variant	Intron 2 of 3	1	NM_020188.5	ENSP00000219400.3
ENSG00000286221	ENST00000650780.1	c.81+4067G>C		intron_variant	Intron 2 of 2			ENSP00000498782.1

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99124 AN: 151890 Hom.: 34094 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.807

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.692

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

GnomAD4 genome AF: 0.652 AC: 99151 AN: 152008 Hom.: 34100 Cov.: 32 AF XY: 0.650 AC XY: 48285 AN XY: 74324

African (AFR) AF: 0.417 AC: 17253 AN: 41418

American (AMR) AF: 0.669 AC: 10215 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.807 AC: 2801 AN: 3470

East Asian (EAS) AF: 0.589 AC: 3042 AN: 5166

South Asian (SAS) AF: 0.799 AC: 3853 AN: 4820

European-Finnish (FIN) AF: 0.663 AC: 6997 AN: 10556

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.772 AC: 52516 AN: 67994

Other (OTH) AF: 0.692 AC: 1462 AN: 2112

Alfa AF: 0.701 Hom.: 4794

Bravo AF: 0.636

Asia WGS AF: 0.702 AC: 2439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.95
DANN	Benign	0.42
PhyloP100		-0.73
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: rs2549855; hg19: chr16-81026852;