Genetic Variant CNNM2:c.*9860C>T (chr10-103087040-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017649.5(CNNM2):c.*9860C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 150,726 control chromosomes in the GnomAD database, including 7,237 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 0.31 ( 7233 hom., cov: 30)

Exomes 𝑓: 0.26 ( 4 hom. )

Consequence

CNNM2
NM_017649.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0480

Variant links:

Genes affected

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]

CNNM2 links:

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]

NT5C2 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNNM2	NM_017649.5 link	c.*9860C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000369878.9	NP_060119.3	Q9H8M5-1
CNNM2	NM_199076.3 link	c.*9860C>T		3_prime_UTR_variant	Exon 7 of 7		NP_951058.1	Q9H8M5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNNM2	ENST00000369878.9 link	c.*9860C>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_017649.5	ENSP00000358894.3		Q9H8M5-1
NT5C2	ENST00000675164.1 link	n.*4190G>A		downstream_gene_variant				ENSP00000502128.1		S4R3A6

Frequencies

GnomAD3 genomes

AF:

0.308

AC:

46368

AN:

150572

Hom.:

7227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.311

Gnomad AMI

AF:

0.333

Gnomad AMR

AF:

0.266

Gnomad ASJ

AF:

0.361

Gnomad EAS

AF:

0.211

Gnomad SAS

AF:

0.248

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.362

Gnomad NFE

AF:

0.325

Gnomad OTH

AF:

0.313

GnomAD4 exome

AF:

0.261

AC:

AN:

Hom.:

Cov.:

AF XY:

0.321

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.167

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.219

AC:

AN:

Other (OTH)

AF:

0.667

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.413

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.308

AC:

46394

AN:

150680

Hom.:

7233

Cov.:

AF XY:

0.304

AC XY:

22355

AN XY:

73460

show subpopulations

African (AFR)

AF:

0.311

AC:

12745

AN:

41038

American (AMR)

AF:

0.266

AC:

4000

AN:

15036

Ashkenazi Jewish (ASJ)

AF:

0.361

AC:

1249

AN:

3462

East Asian (EAS)

AF:

0.211

AC:

1069

AN:

5076

South Asian (SAS)

AF:

0.248

AC:

1185

AN:

4782

European-Finnish (FIN)

AF:

0.296

AC:

3021

AN:

10196

Middle Eastern (MID)

AF:

0.372

AC:

107

AN:

288

European-Non Finnish (NFE)

AF:

0.325

AC:

22064

AN:

67810

Other (OTH)

AF:

0.313

AC:

652

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1581

3162

4743

6324

7905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.318

Hom.:

10055

Bravo

AF:

0.303

Asia WGS

AF:

0.224

AC:

777

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

3.1

(source)

DANN

Benign

0.33

PhyloP100

-0.048

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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chr10-103087040-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over