Variant rs943036 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017649.5(CNNM2):c.2418+20T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 1,550,844 control chromosomes in the GnomAD database, including 123,740 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12617 hom., cov: 32)

Exomes 𝑓: 0.40 ( 111123 hom. )

Consequence

CNNM2
NM_017649.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.68

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:

CNNM2 (HGNC:):

CNNM2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 10-103076290-T-C is Benign according to our data. Variant chr10-103076290-T-C is described in ClinVar as [Benign]. Clinvar id is 1217370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-103076290-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNNM2	NM_017649.5 linkuse as main transcript	c.2418+20T>C		intron_variant		ENST00000369878.9	NP_060119.3	Q9H8M5-1
CNNM2	NM_199076.3 linkuse as main transcript	c.2352+20T>C		intron_variant			NP_951058.1	Q9H8M5-2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CNNM2	ENST00000369878.9 linkuse as main transcript	c.2418+20T>C	intron_variant	1	NM_017649.5	ENSP00000358894.3	Q9H8M5-1
CNNM2	ENST00000433628.2 linkuse as main transcript	c.2352+20T>C	intron_variant	2		ENSP00000392875.2	Q9H8M5-2
CNNM2	ENST00000475511.1 linkuse as main transcript	n.472+20T>C	intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.405

AC:

61500

AN:

151944

Hom.:

12603

Cov.:

show subpopulations

Gnomad AFR

AF:

0.388

Gnomad AMI

AF:

0.349

Gnomad AMR

AF:

0.403

Gnomad ASJ

AF:

0.432

Gnomad EAS

AF:

0.487

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.364

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.415

Gnomad OTH

AF:

0.412

GnomAD3 exomes

AF:

0.409

AC:

64855

AN:

158444

Hom.:

13286

AF XY:

0.409

AC XY:

34169

AN XY:

83540

show subpopulations

Gnomad AFR exome

AF:

0.393

Gnomad AMR exome

AF:

0.412

Gnomad ASJ exome

AF:

0.425

Gnomad EAS exome

AF:

0.492

Gnomad SAS exome

AF:

0.402

Gnomad FIN exome

AF:

0.367

Gnomad NFE exome

AF:

0.407

Gnomad OTH exome

AF:

0.419

GnomAD4 exome

AF:

0.397

AC:

555492

AN:

1398782

Hom.:

111123

Cov.:

AF XY:

0.398

AC XY:

274311

AN XY:

689946

show subpopulations

Gnomad4 AFR exome

AF:

0.386

Gnomad4 AMR exome

AF:

0.418

Gnomad4 ASJ exome

AF:

0.421

Gnomad4 EAS exome

AF:

0.417

Gnomad4 SAS exome

AF:

0.407

Gnomad4 FIN exome

AF:

0.366

Gnomad4 NFE exome

AF:

0.396

Gnomad4 OTH exome

AF:

0.407

GnomAD4 genome

AF:

0.405

AC:

61554

AN:

152062

Hom.:

12617

Cov.:

AF XY:

0.402

AC XY:

29850

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.388

Gnomad4 AMR

AF:

0.403

Gnomad4 ASJ

AF:

0.432

Gnomad4 EAS

AF:

0.486

Gnomad4 SAS

AF:

0.395

Gnomad4 FIN

AF:

0.364

Gnomad4 NFE

AF:

0.415

Gnomad4 OTH

AF:

0.415

Alfa

AF:

0.413

Hom.:

2892

Bravo

AF:

0.408

Asia WGS

AF:

0.403

AC:

1399

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hypomagnesemia, seizures, and intellectual disability 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Renal hypomagnesemia 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.2

DANN

Benign

0.25

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over