10-103087040-C-T

Position:

• chr10-103087040-C-T

Variant summary

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

The ENST00000369878.9(CNNM2):​c.*9860C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 150,726 control chromosomes in the GnomAD database, including 7,237 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 0.31 (7233 hom., cov: 30)
  • Exomes 𝑓: 0.26 (4 hom.)
• Consequence: CNNM2 ENST00000369878.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNNM2	NM_017649.5	c.*9860C>T		3_prime_UTR_variant	8/8	ENST00000369878.9	NP_060119.3
CNNM2	NM_199076.3	c.*9860C>T		3_prime_UTR_variant	7/7		NP_951058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNNM2	ENST00000369878.9	c.*9860C>T		3_prime_UTR_variant	8/8	1	NM_017649.5	ENSP00000358894	P4

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46368 AN: 150572 Hom.: 7227 Cov.: 30

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.362

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.313

GnomAD4 exome AF: 0.261 AC: 12 AN: 46 Hom.: 4 Cov.: 0 AF XY: 0.321 AC XY: 9 AN XY: 28

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.308 AC: 46394 AN: 150680 Hom.: 7233 Cov.: 30 AF XY: 0.304 AC XY: 22355 AN XY: 73460

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.313

Alfa AF: 0.318 Hom.: 7699

Bravo AF: 0.303

Asia WGS AF: 0.224 AC: 777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.33

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: rs11191549; hg19: chr10-104846797;