10-103053140-A-G

Position:

• chr10-103053140-A-G

Variant summary

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

The ENST00000369878.9(CNNM2):​c.1766-1189A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,062 control chromosomes in the GnomAD database, including 12,420 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 0.40 (12420 hom., cov: 32)
• Consequence: CNNM2 ENST00000369878.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.581

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=-0.94).
• 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	Protein	UniProt
CNNM2	NM_017649.5	c.1766-1189A>G		intron_variant		ENST00000369878.9	NP_060119.3
CNNM2	NM_199076.3	c.1766-1189A>G		intron_variant			NP_951058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNNM2	ENST00000369878.9	c.1766-1189A>G		intron_variant		1	NM_017649.5	ENSP00000358894	P4
CNNM2	ENST00000433628.2	c.1766-1189A>G		intron_variant		2		ENSP00000392875	A1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60994 AN: 151942 Hom.: 12405 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.401 AC: 61049 AN: 152062 Hom.: 12420 Cov.: 32 AF XY: 0.399 AC XY: 29619 AN XY: 74326

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.415

Alfa AF: 0.409 Hom.: 2094

Bravo AF: 0.404

Asia WGS AF: 0.403 AC: 1397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.51
DANN	Benign	0.48

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: rs10883824; hg19: chr10-104812897;