rs7092200

Positions:

• chr10-103085115-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017649.5(CNNM2):​c.*7935T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,920 control chromosomes in the GnomAD database, including 13,591 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 0.42 (13588 hom., cov: 31)
  • Exomes 𝑓: 0.36 (3 hom.)
• Consequence: CNNM2 NM_017649.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNNM2	NM_017649.5	c.*7935T>C		3_prime_UTR_variant	8/8	ENST00000369878.9
CNNM2	NM_199076.3	c.*7935T>C		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNNM2	ENST00000369878.9	c.*7935T>C		3_prime_UTR_variant	8/8	1	NM_017649.5	P4

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63723 AN: 151774 Hom.: 13573 Cov.: 31

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.432

GnomAD4 exome AF: 0.357 AC: 10 AN: 28 Hom.: 3 Cov.: 0 AF XY: 0.300 AC XY: 6 AN XY: 20

Gnomad4 AMR exome AF: 0.00

Gnomad4 NFE exome AF: 0.350

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.420 AC: 63777 AN: 151892 Hom.: 13588 Cov.: 31 AF XY: 0.416 AC XY: 30894 AN XY: 74230

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.435

Alfa AF: 0.425 Hom.: 6550

Bravo AF: 0.423

Asia WGS AF: 0.410 AC: 1423 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	0.19
DANN	Benign	0.31

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

Publications

LitVar

Other links and lift over

dbSNP: rs7092200; hg19: chr10-104844872;