rs1538204

Variant names:

• chr10-102974136-T-A
• rs1538204
• NM_017649.5:c.1621+54035T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-102974136-T-A
• chr10-102974136-T-C
• chr10-102974136-T-G

Variant summary

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

The NM_017649.5(CNNM2):​c.1621+54035T>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 152,064 control chromosomes in the GnomAD database, including 12,865 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 (12865 hom., cov: 32)
• Consequence: CNNM2 NM_017649.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 8 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=-0.88).
• 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.1621+54035T>A		intron_variant	Intron 1 of 7	ENST00000369878.9	NP_060119.3
CNNM2	NM_199076.3	c.1621+54035T>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.1621+54035T>A		intron_variant	Intron 1 of 7	1	NM_017649.5	ENSP00000358894.3
CNNM2	ENST00000433628.2	c.1621+54035T>A		intron_variant	Intron 1 of 6	2		ENSP00000392875.2

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61949 AN: 151946 Hom.: 12852 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.368

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: 62005 AN: 152064 Hom.: 12865 Cov.: 32 AF XY: 0.406 AC XY: 30205 AN XY: 74346

African (AFR) AF: 0.378 AC: 15660 AN: 41452

American (AMR) AF: 0.401 AC: 6120 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1516 AN: 3464

East Asian (EAS) AF: 0.559 AC: 2885 AN: 5162

South Asian (SAS) AF: 0.449 AC: 2166 AN: 4824

European-Finnish (FIN) AF: 0.368 AC: 3900 AN: 10586

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

European-Non Finnish (NFE) AF: 0.418 AC: 28417 AN: 67978

Other (OTH) AF: 0.422 AC: 892 AN: 2112

Alfa AF: 0.422 Hom.: 1700

Bravo AF: 0.408

Asia WGS AF: 0.467 AC: 1619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.32
DANN	Benign	0.48
PhyloP100		-1.3
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: rs1538204; hg19: chr10-104733893;