rs7914558

Variant names:

• chr10-103016151-G-A
• rs7914558
• NM_017649.5:c.1622-33556G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-103016151-G-A
• chr10-103016151-G-C
• chr10-103016151-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017649.5(CNNM2):​c.1622-33556G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,480 control chromosomes in the GnomAD database, including 12,724 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 (12724 hom., cov: 29)
• Consequence: CNNM2 NM_017649.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309
• Publications: 81 publications found

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 Gene-Disease associations (from GenCC):

• hypomagnesemia, seizures, and intellectual disability 1

  Inheritance: AR, SD, AD Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Illumina, Labcorp Genetics (formerly Invitae)
• renal hypomagnesemia 6

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• familial primary hypomagnesemia with normocalciuria and normocalcemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNNM2	NM_017649.5	c.1622-33556G>A		intron_variant	Intron 1 of 7	ENST00000369878.9	NP_060119.3
CNNM2	NM_199076.3	c.1622-33556G>A		intron_variant	Intron 1 of 6		NP_951058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNNM2	ENST00000369878.9	c.1622-33556G>A		intron_variant	Intron 1 of 7	1	NM_017649.5	ENSP00000358894.3
CNNM2	ENST00000433628.2	c.1622-33556G>A		intron_variant	Intron 1 of 6	2		ENSP00000392875.2

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61477 AN: 151362 Hom.: 12712 Cov.: 29

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.406 AC: 61531 AN: 151480 Hom.: 12724 Cov.: 29 AF XY: 0.404 AC XY: 29924 AN XY: 73982

African (AFR) AF: 0.373 AC: 15398 AN: 41282

American (AMR) AF: 0.400 AC: 6083 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1514 AN: 3464

East Asian (EAS) AF: 0.559 AC: 2857 AN: 5110

South Asian (SAS) AF: 0.450 AC: 2153 AN: 4786

European-Finnish (FIN) AF: 0.367 AC: 3834 AN: 10450

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28361 AN: 67866

Other (OTH) AF: 0.420 AC: 884 AN: 2104

Alfa AF: 0.416 Hom.: 42528

Bravo AF: 0.407

Asia WGS AF: 0.470 AC: 1631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.40
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7914558; hg19: chr10-104775908;