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GeneBe

10-102918371-A-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_017649.5(CNNM2):c.-110A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,494,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

CNNM2
NM_017649.5 5_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0940
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 10-102918371-A-T is Benign according to our data. Variant chr10-102918371-A-T is described in ClinVar as [Benign]. Clinvar id is 298632.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000112 (17/152314) while in subpopulation SAS AF= 0.00352 (17/4834). AF 95% confidence interval is 0.00224. There are 0 homozygotes in gnomad4. There are 13 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CNNM2NM_017649.5 linkuse as main transcriptc.-110A>T 5_prime_UTR_variant 1/8 ENST00000369878.9
CNNM2NM_199076.3 linkuse as main transcriptc.-110A>T 5_prime_UTR_variant 1/7
CNNM2NM_199077.3 linkuse as main transcriptc.-110A>T 5_prime_UTR_variant 1/2
LOC107984265NR_160733.1 linkuse as main transcript upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CNNM2ENST00000369878.9 linkuse as main transcriptc.-110A>T 5_prime_UTR_variant 1/81 NM_017649.5 P4Q9H8M5-1
CNNM2ENST00000369875.3 linkuse as main transcriptc.-110A>T 5_prime_UTR_variant 1/21 Q9H8M5-3
CNNM2ENST00000433628.2 linkuse as main transcriptc.-110A>T 5_prime_UTR_variant 1/72 A1Q9H8M5-2
ENST00000652934.1 linkuse as main transcript upstream_gene_variant

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152196
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00351
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.000144
AC:
193
AN:
1342202
Hom.:
0
Cov.:
30
AF XY:
0.000209
AC XY:
138
AN XY:
661758
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000322
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152314
Hom.:
0
Cov.:
32
AF XY:
0.000175
AC XY:
13
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00352
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Renal hypomagnesemia 6 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
Cadd
Benign
10
Dann
Benign
0.92
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs555951352; hg19: chr10-104678128; API