rs1890185

Variant names:

• chr10-102988961-A-G
• rs1890185
• NM_017649.5:c.1622-60746A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-102988961-A-G
• chr10-102988961-A-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.1622-60746A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,028 control chromosomes in the GnomAD database, including 12,859 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 (12859 hom., cov: 32)
• Consequence: CNNM2 NM_017649.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.508
• Publications: 25 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017649.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNNM2	NM_017649.5	MANE Select	c.1622-60746A>G		intron	N/A	NP_060119.3
	CNNM2	NM_199076.3		c.1622-60746A>G		intron	N/A	NP_951058.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNNM2	ENST00000369878.9	TSL:1 MANE Select	c.1622-60746A>G		intron	N/A	ENSP00000358894.3
	CNNM2	ENST00000433628.2	TSL:2	c.1622-60746A>G		intron	N/A	ENSP00000392875.2

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61918 AN: 151910 Hom.: 12847 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.408 AC: 61971 AN: 152028 Hom.: 12859 Cov.: 32 AF XY: 0.406 AC XY: 30180 AN XY: 74328

African (AFR) AF: 0.377 AC: 15614 AN: 41462

American (AMR) AF: 0.402 AC: 6129 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1516 AN: 3466

East Asian (EAS) AF: 0.558 AC: 2892 AN: 5180

South Asian (SAS) AF: 0.450 AC: 2165 AN: 4808

European-Finnish (FIN) AF: 0.369 AC: 3894 AN: 10566

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28420 AN: 67970

Other (OTH) AF: 0.423 AC: 892 AN: 2110

Alfa AF: 0.422 Hom.: 1707

Bravo AF: 0.409

Asia WGS AF: 0.470 AC: 1632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.3
DANN	Benign	0.66
PhyloP100		-0.51
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: rs1890185; hg19: chr10-104748718;