rs3781285

Variant names:

• chr10-103065908-C-G
• rs3781285
• NM_017649.5:c.2074-2721C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-103065908-C-G
• chr10-103065908-C-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.2074-2721C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0824 in 152,198 control chromosomes in the GnomAD database, including 800 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 0.082 (800 hom., cov: 32)
• Consequence: CNNM2 NM_017649.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.44
• Publications: 18 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNNM2	NM_017649.5	c.2074-2721C>G		intron_variant	Intron 4 of 7	ENST00000369878.9	NP_060119.3
CNNM2	NM_199076.3	c.2074-2721C>G		intron_variant	Intron 4 of 6		NP_951058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNNM2	ENST00000369878.9	c.2074-2721C>G		intron_variant	Intron 4 of 7	1	NM_017649.5	ENSP00000358894.3
CNNM2	ENST00000433628.2	c.2074-2721C>G		intron_variant	Intron 4 of 6	2		ENSP00000392875.2

Frequencies

GnomAD3 genomes AF: 0.0824 AC: 12534 AN: 152080 Hom.: 796 Cov.: 32

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0689

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.0743

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0895

Gnomad OTH AF: 0.0951

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

GnomAD4 genome AF: 0.0824 AC: 12543 AN: 152198 Hom.: 800 Cov.: 32 AF XY: 0.0848 AC XY: 6311 AN XY: 74390

African (AFR) AF: 0.0196 AC: 815 AN: 41554

American (AMR) AF: 0.134 AC: 2052 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0689 AC: 239 AN: 3468

East Asian (EAS) AF: 0.279 AC: 1438 AN: 5162

South Asian (SAS) AF: 0.183 AC: 879 AN: 4812

European-Finnish (FIN) AF: 0.0743 AC: 788 AN: 10604

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0896 AC: 6089 AN: 67988

Other (OTH) AF: 0.0984 AC: 208 AN: 2114

Alfa AF: 0.0439 Hom.: 35

Bravo AF: 0.0845

Asia WGS AF: 0.195 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.55
PhyloP100		2.4
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: rs3781285; hg19: chr10-104825665;