rs2063239

Variant names:

• chr12-82880462-G-A
• rs2063239
• NM_152588.3:c.655-15356G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-82880462-G-A
• chr12-82880462-G-T

Variant summary

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

The NM_152588.3(TMTC2):​c.655-15356G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,020 control chromosomes in the GnomAD database, including 13,817 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 0.43 (13817 hom., cov: 32)
• Consequence: TMTC2 NM_152588.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 5 publications found

Genes affected

TMTC2 (HGNC:25440): (transmembrane O-mannosyltransferase targeting cadherins 2) The protein encoded by this gene is an integral membrane protein localized to the endoplasmic reticulum (ER). The encoded protein contains many tetratricopeptide repeats, sequences known for being involved in protein-protein interactions. This protein binds both the calcium uptake pump SERCA2B and the carbohydrate-binding chaperone calnexin, and it appears to play a role in calcium homeostasis in the ER. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

TMTC2 Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMTC2	NM_152588.3	c.655-15356G>A		intron_variant	Intron 2 of 11	ENST00000321196.8	NP_689801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMTC2	ENST00000321196.8	c.655-15356G>A		intron_variant	Intron 2 of 11	1	NM_152588.3	ENSP00000322300.3

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64651 AN: 151902 Hom.: 13806 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.425 AC: 64672 AN: 152020 Hom.: 13817 Cov.: 32 AF XY: 0.426 AC XY: 31691 AN XY: 74334

African (AFR) AF: 0.383 AC: 15873 AN: 41468

American (AMR) AF: 0.475 AC: 7258 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1716 AN: 3470

East Asian (EAS) AF: 0.410 AC: 2115 AN: 5160

South Asian (SAS) AF: 0.435 AC: 2094 AN: 4818

European-Finnish (FIN) AF: 0.408 AC: 4304 AN: 10552

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.437 AC: 29719 AN: 67962

Other (OTH) AF: 0.456 AC: 961 AN: 2106

Alfa AF: 0.433 Hom.: 53906

Bravo AF: 0.431

Asia WGS AF: 0.414 AC: 1440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.56
DANN	Benign	0.41
PhyloP100		-1.0
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: rs2063239; hg19: chr12-83274241;