NM_017649.5:c.*12179G>T

Variant names:

• chr10-103089359-G-T
• rs10786736
• NM_017649.5:c.*12179G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017649.5(CNNM2):​c.*12179G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNNM2 NM_017649.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275
• Publications: 29 publications found

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]

NT5C2 (HGNC:8022): (5'-nucleotidase, cytosolic II) This gene encodes a hydrolase that serves as an important role in cellular purine metabolism by acting primarily on inosine 5'-monophosphate and other purine nucleotides. [provided by RefSeq, Oct 2011]

NT5C2 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia 45

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNNM2	NM_017649.5	c.*12179G>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000369878.9	NP_060119.3
NT5C2	NM_001351169.2	c.*313C>A		3_prime_UTR_variant	Exon 19 of 19	ENST00000404739.8	NP_001338098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNNM2	ENST00000369878.9	c.*12179G>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_017649.5	ENSP00000358894.3
NT5C2	ENST00000404739.8	c.*313C>A		3_prime_UTR_variant	Exon 19 of 19	1	NM_001351169.2	ENSP00000383960.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 125230 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 60568

African (AFR) AF: 0.00 AC: 0 AN: 5104

American (AMR) AF: 0.00 AC: 0 AN: 5032

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6204

East Asian (EAS) AF: 0.00 AC: 0 AN: 12676

South Asian (SAS) AF: 0.00 AC: 0 AN: 3116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 664

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 79506

Other (OTH) AF: 0.00 AC: 0 AN: 9302

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.8
DANN	Benign	0.60
PhyloP100		0.28

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

Other links and lift over

dbSNP: rs10786736; hg19: chr10-104849116;