rs12573221

chr10-103089387-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017649.5(CNNM2):c.*12207A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0225 in 310,428 control chromosomes in the GnomAD database, including 150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.023 (78 hom., cov: 32)
  • Exomes 𝑓: 0.022 (72 hom.)
• Consequence: CNNM2 NM_017649.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.198

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-103089387-A-C is Benign according to our data. Variant chr10-103089387-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1178021.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NT5C2	NM_001351169.2	c.*285T>G		3_prime_UTR_variant	19/19	ENST00000404739.8
CNNM2	NM_017649.5	c.*12207A>C		3_prime_UTR_variant	8/8	ENST00000369878.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNNM2	ENST00000369878.9	c.*12207A>C		3_prime_UTR_variant	8/8	1	NM_017649.5	P4
NT5C2	ENST00000404739.8	c.*285T>G		3_prime_UTR_variant	19/19	1	NM_001351169.2	P1

Frequencies

GnomAD3 genomes AF: 0.0226 AC: 3442 AN: 152152 Hom.: 78 Cov.: 32

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.0446

Gnomad EAS AF: 0.0520

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.00641

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0170

Gnomad OTH AF: 0.0225

GnomAD4 exome AF: 0.0224 AC: 3547 AN: 158158 Hom.: 72 Cov.: 4 AF XY: 0.0227 AC XY: 1771 AN XY: 77910

Gnomad4 AFR exome AF: 0.0262

Gnomad4 AMR exome AF: 0.00925

Gnomad4 ASJ exome AF: 0.0391

Gnomad4 EAS exome AF: 0.0424

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.00918

Gnomad4 NFE exome AF: 0.0168

Gnomad4 OTH exome AF: 0.0199

GnomAD4 genome AF: 0.0226 AC: 3435 AN: 152270 Hom.: 78 Cov.: 32 AF XY: 0.0233 AC XY: 1738 AN XY: 74450

Gnomad4 AFR AF: 0.0250

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.0446

Gnomad4 EAS AF: 0.0519

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.00641

Gnomad4 NFE AF: 0.0170

Gnomad4 OTH AF: 0.0223

Alfa AF: 0.0197 Hom.: 19

Bravo AF: 0.0209

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	5.9
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12573221; hg19: chr10-104849144;