rs11191549

Variant names:

• chr10-103087040-C-T
• rs11191549
• NM_017649.5:c.*9860C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017649.5(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 NM_017649.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480
• Publications: 14 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):

• complex hereditary spastic paraplegia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• 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: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017649.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNNM2	NM_017649.5	MANE Select	c.*9860C>T		3_prime_UTR	Exon 8 of 8	NP_060119.3
	CNNM2	NM_199076.3		c.*9860C>T		3_prime_UTR	Exon 7 of 7	NP_951058.1	Q9H8M5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNNM2	ENST00000369878.9	TSL:1 MANE Select	c.*9860C>T		3_prime_UTR	Exon 8 of 8	ENSP00000358894.3	Q9H8M5-1
	NT5C2	ENST00000874297.1		c.*2632G>A		downstream_gene	N/A	ENSP00000544356.1
	NT5C2	ENST00000675164.1		n.*4190G>A		downstream_gene	N/A	ENSP00000502128.1	S4R3A6

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.167 AC: 1 AN: 6

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.219 AC: 7 AN: 32

Other (OTH) AF: 0.667 AC: 4 AN: 6

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

African (AFR) AF: 0.311 AC: 12745 AN: 41038

American (AMR) AF: 0.266 AC: 4000 AN: 15036

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1249 AN: 3462

East Asian (EAS) AF: 0.211 AC: 1069 AN: 5076

South Asian (SAS) AF: 0.248 AC: 1185 AN: 4782

European-Finnish (FIN) AF: 0.296 AC: 3021 AN: 10196

Middle Eastern (MID) AF: 0.372 AC: 107 AN: 288

European-Non Finnish (NFE) AF: 0.325 AC: 22064 AN: 67810

Other (OTH) AF: 0.313 AC: 652 AN: 2086

Alfa AF: 0.318 Hom.: 10055

Bravo AF: 0.303

Asia WGS AF: 0.224 AC: 777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.33
PhyloP100		-0.048
Mutation Taster		=100/0	polymorphism (auto)

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: rs11191549; hg19: chr10-104846797;