rs2549855

Positions:

• chr16-80993247-C-G

Variant summary

Our verdict is Benign. Variant got -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

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CMC2	NM_020188.5	c.81+4067G>C		intron_variant		ENST00000219400.8	NP_064573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMC2	ENST00000219400.8	c.81+4067G>C		intron_variant		1	NM_020188.5	ENSP00000219400	P1

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

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.807

Gnomad4 EAS AF: 0.589

Gnomad4 SAS AF: 0.799

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.772

Gnomad4 OTH AF: 0.692

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2549855; hg19: chr16-81026852;