rs8139

Variant names:

• chr10-103088366-G-A
• rs8139
• NM_017649.5:c.*11186G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-103088366-G-A
• chr10-103088366-G-C

Variant summary

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

The NM_017649.5(CNNM2):​c.*11186G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,024 control chromosomes in the GnomAD database, including 12,693 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 0.41 (12693 hom., cov: 32)
  • Exomes 𝑓: 0.21 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNNM2 NM_017649.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272
• Publications: 21 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 (EAS) allele frequency at 95% confidence interval = 0.469 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.*11186G>A		3_prime_UTR	Exon 8 of 8	NP_060119.3
	NT5C2	NM_001351169.2	MANE Select	c.*1306C>T		3_prime_UTR	Exon 19 of 19	NP_001338098.1	P49902-1
	CNNM2	NM_199076.3		c.*11186G>A		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.*11186G>A		3_prime_UTR	Exon 8 of 8	ENSP00000358894.3	Q9H8M5-1
	NT5C2	ENST00000404739.8	TSL:1 MANE Select	c.*1306C>T		3_prime_UTR	Exon 19 of 19	ENSP00000383960.3	P49902-1
	NT5C2	ENST00000343289.9	TSL:1	c.*1306C>T		3_prime_UTR	Exon 18 of 18	ENSP00000339479.5	P49902-1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61666 AN: 151906 Hom.: 12682 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.416

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.214 AC: 3 AN: 14 Hom.: 1 Cov.: 0 AF XY: 0.200 AC XY: 2 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

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

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.125 AC: 1 AN: 8

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.406 AC: 61717 AN: 152024 Hom.: 12693 Cov.: 32 AF XY: 0.404 AC XY: 29986 AN XY: 74294

African (AFR) AF: 0.388 AC: 16096 AN: 41466

American (AMR) AF: 0.403 AC: 6154 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1496 AN: 3468

East Asian (EAS) AF: 0.485 AC: 2510 AN: 5172

South Asian (SAS) AF: 0.429 AC: 2068 AN: 4822

European-Finnish (FIN) AF: 0.365 AC: 3855 AN: 10554

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28207 AN: 67944

Other (OTH) AF: 0.418 AC: 884 AN: 2114

Alfa AF: 0.404 Hom.: 17082

Bravo AF: 0.408

Asia WGS AF: 0.423 AC: 1466 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	2.6
DANN	Benign	0.76
PhyloP100		0.27
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: rs8139; hg19: chr10-104848123; COSMIC: COSV58419314; COSMIC: COSV58419314;