rs2296569

Positions:

• chr10-103076754-A-G

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.2419-217A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,226 control chromosomes in the GnomAD database, including 1,532 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (1532 hom., cov: 32)
• Consequence: CNNM2 NM_017649.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.357

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 10-103076754-A-G is Benign according to our data. Variant chr10-103076754-A-G is described in ClinVar as [Benign]. Clinvar id is 1243956.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNNM2	NM_017649.5	c.2419-217A>G		intron_variant		ENST00000369878.9	NP_060119.3
CNNM2	NM_199076.3	c.2353-217A>G		intron_variant			NP_951058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNNM2	ENST00000369878.9	c.2419-217A>G		intron_variant		1	NM_017649.5	ENSP00000358894	P4
CNNM2	ENST00000433628.2	c.2353-217A>G		intron_variant		2		ENSP00000392875	A1
CNNM2	ENST00000475511.1	n.473-217A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18787 AN: 152108 Hom.: 1533 Cov.: 32

Gnomad AFR AF: 0.0322

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0843

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.0990

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.123 AC: 18778 AN: 152226 Hom.: 1532 Cov.: 32 AF XY: 0.122 AC XY: 9085 AN XY: 74418

Gnomad4 AFR AF: 0.0321

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0842

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.0980

Alfa AF: 0.163 Hom.: 3035

Bravo AF: 0.111

Asia WGS AF: 0.0390 AC: 139 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	10
DANN	Benign	0.58

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: rs2296569; hg19: chr10-104836511;