rs10883817

Variant names:

• chr10-102995674-G-A
• rs10883817
• NM_017649.5:c.1622-54033G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-102995674-G-A
• chr10-102995674-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.1622-54033G>A 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 148,474 control chromosomes in the GnomAD database, including 12,360 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 (12360 hom., cov: 28)
• Consequence: CNNM2 NM_017649.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.680
• Publications: 23 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNNM2	NM_017649.5	c.1622-54033G>A		intron_variant	Intron 1 of 7	ENST00000369878.9	NP_060119.3
CNNM2	NM_199076.3	c.1622-54033G>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.1622-54033G>A		intron_variant	Intron 1 of 7	1	NM_017649.5	ENSP00000358894.3
CNNM2	ENST00000433628.2	c.1622-54033G>A		intron_variant	Intron 1 of 6	2		ENSP00000392875.2

Frequencies

GnomAD3 genomes AF: 0.408 AC: 60557 AN: 148376 Hom.: 12349 Cov.: 28

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.445

Gnomad NFE AF: 0.419

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: 60606 AN: 148474 Hom.: 12360 Cov.: 28 AF XY: 0.407 AC XY: 29422 AN XY: 72204

African (AFR) AF: 0.381 AC: 15228 AN: 39986

American (AMR) AF: 0.411 AC: 6041 AN: 14704

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1508 AN: 3462

East Asian (EAS) AF: 0.490 AC: 2474 AN: 5052

South Asian (SAS) AF: 0.432 AC: 2043 AN: 4728

European-Finnish (FIN) AF: 0.381 AC: 3753 AN: 9846

Middle Eastern (MID) AF: 0.455 AC: 130 AN: 286

European-Non Finnish (NFE) AF: 0.419 AC: 28240 AN: 67438

Other (OTH) AF: 0.422 AC: 870 AN: 2062

Alfa AF: 0.345 Hom.: 1477

Bravo AF: 0.403

Asia WGS AF: 0.425 AC: 1475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.31
DANN	Benign	0.59
PhyloP100		-0.68
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: rs10883817; hg19: chr10-104755431;