rs8139

chr10-103088366-G-Achr10-103088366-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017649.5(CNNM2):c.*11186G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,024 control chromosomes in the GnomAD database, including 12,693 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 0.41 (12693 hom., cov: 32)
  • Exomes 𝑓: 0.21 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNNM2 NM_017649.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272

Genes affected

NT5C2 (HGNC:8022): (5'-nucleotidase, cytosolic II) This gene encodes a hydrolase that serves as an important role in cellular purine metabolism by acting primarily on inosine 5'-monophosphate and other purine nucleotides. [provided by RefSeq, Oct 2011]

CNNM2 (HGNC:103): (cyclin and CBS domain divalent metal cation transport mediator 2) This gene encodes a member of the ancient conserved domain containing protein family. Members of this protein family contain a cyclin box motif and have structural similarity to the cyclins. The encoded protein may play an important role in magnesium homeostasis by mediating the epithelial transport and renal reabsorption of Mg2+. Mutations in this gene are associated with renal hypomagnesemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NT5C2	NM_001351169.2	c.*1306C>T		3_prime_UTR_variant	19/19	ENST00000404739.8
CNNM2	NM_017649.5	c.*11186G>A		3_prime_UTR_variant	8/8	ENST00000369878.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNNM2	ENST00000369878.9	c.*11186G>A		3_prime_UTR_variant	8/8	1	NM_017649.5	P4
NT5C2	ENST00000404739.8	c.*1306C>T		3_prime_UTR_variant	19/19	1	NM_001351169.2	P1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61666 AN: 151906 Hom.: 12682 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.416

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.214 AC: 3 AN: 14 Hom.: 1 Cov.: 0 AF XY: 0.200 AC XY: 2 AN XY: 10

Gnomad4 ASJ exome AF: 0.00

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.406 AC: 61717 AN: 152024 Hom.: 12693 Cov.: 32 AF XY: 0.404 AC XY: 29986 AN XY: 74294

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.418

Alfa AF: 0.401 Hom.: 11856

Bravo AF: 0.408

Asia WGS AF: 0.423 AC: 1466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.6
Dann	Benign	0.76

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: rs8139; hg19: chr10-104848123; COSMIC: COSV58419314; COSMIC: COSV58419314;