dbSNP rs8139: CNNM2:c.*11186G>A (chr10-103088366-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.272

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
CNNM2	NM_017649.5 link	c.*11186G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000369878.9	NP_060119.3	Q9H8M5-1
NT5C2	NM_001351169.2 link	c.*1306C>T		3_prime_UTR_variant	Exon 19 of 19	ENST00000404739.8	NP_001338098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNNM2	ENST00000369878.9 link	c.*11186G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_017649.5	ENSP00000358894.3		Q9H8M5-1
NT5C2	ENST00000404739 link	c.*1306C>T		3_prime_UTR_variant	Exon 19 of 19	1	NM_001351169.2	ENSP00000383960.3		P49902-1

Frequencies

GnomAD3 genomes

AF:

0.406

AC:

61666

AN:

151906

Hom.:

12682

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.200

AC XY:

AN XY:

show subpopulations

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.:

AF XY:

0.404

AC XY:

29986

AN XY:

74294

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over