rs1926032

Positions:

• chr10-103069712-C-T

Variant summary

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

The NM_017649.5(CNNM2):​c.2167+990C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0735 in 152,252 control chromosomes in the GnomAD database, including 627 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 0.073 (627 hom., cov: 33)
• Consequence: CNNM2 NM_017649.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNNM2	NM_017649.5	c.2167+990C>T		intron_variant		ENST00000369878.9
CNNM2	NM_199076.3	c.2167+990C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNNM2	ENST00000369878.9	c.2167+990C>T		intron_variant		1	NM_017649.5	P4
CNNM2	ENST00000433628.2	c.2167+990C>T		intron_variant		2		A1
CNNM2	ENST00000475511.1	n.287+990C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0734 AC: 11165 AN: 152134 Hom.: 619 Cov.: 33

Gnomad AFR AF: 0.0358

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0605

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0602

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0692

Gnomad OTH AF: 0.0799

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

GnomAD4 genome AF: 0.0735 AC: 11188 AN: 152252 Hom.: 627 Cov.: 33 AF XY: 0.0752 AC XY: 5596 AN XY: 74442

Gnomad4 AFR AF: 0.0359

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.0605

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.0602

Gnomad4 NFE AF: 0.0692

Gnomad4 OTH AF: 0.0838

Alfa AF: 0.0669 Hom.: 58

Bravo AF: 0.0771

Asia WGS AF: 0.186 AC: 644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.34
DANN	Benign	0.84

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: rs1926032; hg19: chr10-104829469;