chr16-80988627-T-C

Variant names:

• chr16-80988627-T-C
• rs2549833
• NM_020188.5:c.82-6750A>G

Variant summary

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

The NM_020188.5(CMC2):​c.82-6750A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 699,818 control chromosomes in the GnomAD database, including 185,699 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 (34020 hom., cov: 31)
  • Exomes 𝑓: 0.74 (151679 hom.)
• Consequence: CMC2 NM_020188.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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=-1.02).
• 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.82-6750A>G		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.82-6750A>G		intron_variant	Intron 2 of 3	1	NM_020188.5	ENSP00000219400.3
ENSG00000286221	ENST00000650780.1	c.81+8687A>G		intron_variant	Intron 2 of 2			ENSP00000498782.1

Frequencies

GnomAD3 genomes AF: 0.652 AC: 98988 AN: 151808 Hom.: 34014 Cov.: 31

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.807

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.692

GnomAD2 exomes AF: 0.715 AC: 90189 AN: 126132 AF XY: 0.731

Gnomad AFR exome AF: 0.404

Gnomad AMR exome AF: 0.614

Gnomad ASJ exome AF: 0.813

Gnomad EAS exome AF: 0.592

Gnomad FIN exome AF: 0.674

Gnomad NFE exome AF: 0.777

Gnomad OTH exome AF: 0.743

GnomAD4 exome AF: 0.738 AC: 404344 AN: 547892 Hom.: 151679 Cov.: 0 AF XY: 0.747 AC XY: 221558 AN XY: 296588

African (AFR) AF: 0.413 AC: 6451 AN: 15606

American (AMR) AF: 0.617 AC: 21120 AN: 34226

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 16178 AN: 19970

East Asian (EAS) AF: 0.556 AC: 17811 AN: 32046

South Asian (SAS) AF: 0.805 AC: 50047 AN: 62168

European-Finnish (FIN) AF: 0.682 AC: 22622 AN: 33160

Middle Eastern (MID) AF: 0.763 AC: 3090 AN: 4052

European-Non Finnish (NFE) AF: 0.774 AC: 244853 AN: 316194

Other (OTH) AF: 0.728 AC: 22172 AN: 30470

GnomAD4 genome AF: 0.652 AC: 99015 AN: 151926 Hom.: 34020 Cov.: 31 AF XY: 0.649 AC XY: 48201 AN XY: 74254

African (AFR) AF: 0.416 AC: 17198 AN: 41378

American (AMR) AF: 0.667 AC: 10185 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.807 AC: 2800 AN: 3468

East Asian (EAS) AF: 0.590 AC: 3046 AN: 5166

South Asian (SAS) AF: 0.799 AC: 3841 AN: 4808

European-Finnish (FIN) AF: 0.663 AC: 6973 AN: 10514

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.772 AC: 52499 AN: 67996

Other (OTH) AF: 0.693 AC: 1463 AN: 2112

Alfa AF: 0.715 Hom.: 7324

Bravo AF: 0.635

Asia WGS AF: 0.702 AC: 2440 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.43
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

Publications

LitVar

Other links and lift over

dbSNP: rs2549833; hg19: chr16-81022232;