2-201628160-TAAA-TA

Variant names:

• chr2-201628160-TAA-T
• rs555284377
• NM_001044385.3:c.870-13_870-12delTT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001044385.3(TMEM237):​c.870-13_870-12delTT variant causes a intron change. The variant allele was found at a frequency of 0.0501 in 1,585,366 control chromosomes in the GnomAD database, including 2,367 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.067 (485 hom., cov: 31)
  • Exomes 𝑓: 0.048 (1882 hom.)
• Consequence: TMEM237 NM_001044385.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 4.95
• Publications: 0 publications found

Genes affected

TMEM237 (HGNC:14432): (transmembrane protein 237) The protein encoded by this gene is a tetraspanin protein that is thought to be involved in WNT signaling. Defects in this gene are a cause of Joubert syndrome-14. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

TMEM237 Gene-Disease associations (from GenCC):

• Joubert syndrome 14

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome with oculorenal defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome with renal defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Meckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 2-201628160-TAA-T is Benign according to our data. Variant chr2-201628160-TAA-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM237	NM_001044385.3	c.870-13_870-12delTT		intron_variant	Intron 9 of 12	ENST00000409883.7	NP_001037850.1
TMEM237	NM_152388.4	c.846-13_846-12delTT		intron_variant	Intron 9 of 12		NP_689601.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM237	ENST00000409883.7	c.870-13_870-12delTT		intron_variant	Intron 9 of 12	5	NM_001044385.3	ENSP00000386264.2

Frequencies

GnomAD3 genomes AF: 0.0671 AC: 10204 AN: 152114 Hom.: 484 Cov.: 31

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.0535

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.0157

Gnomad FIN AF: 0.0137

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0545

Gnomad OTH AF: 0.0626

GnomAD2 exomes AF: 0.0428 AC: 9116 AN: 212796 AF XY: 0.0424

Gnomad AFR exome AF: 0.129

Gnomad AMR exome AF: 0.0324

Gnomad ASJ exome AF: 0.0508

Gnomad EAS exome AF: 0.000188

Gnomad FIN exome AF: 0.0173

Gnomad NFE exome AF: 0.0539

Gnomad OTH exome AF: 0.0444

GnomAD4 exome AF: 0.0483 AC: 69239 AN: 1433136 Hom.: 1882 AF XY: 0.0474 AC XY: 33704 AN XY: 711262

African (AFR) AF: 0.126 AC: 4125 AN: 32808

American (AMR) AF: 0.0339 AC: 1418 AN: 41884

Ashkenazi Jewish (ASJ) AF: 0.0496 AC: 1261 AN: 25448

East Asian (EAS) AF: 0.000102 AC: 4 AN: 39044

South Asian (SAS) AF: 0.0175 AC: 1439 AN: 82462

European-Finnish (FIN) AF: 0.0173 AC: 898 AN: 52038

Middle Eastern (MID) AF: 0.0469 AC: 268 AN: 5718

European-Non Finnish (NFE) AF: 0.0521 AC: 56984 AN: 1094498

Other (OTH) AF: 0.0480 AC: 2842 AN: 59236

GnomAD4 genome AF: 0.0671 AC: 10211 AN: 152230 Hom.: 485 Cov.: 31 AF XY: 0.0648 AC XY: 4820 AN XY: 74424

African (AFR) AF: 0.123 AC: 5122 AN: 41526

American (AMR) AF: 0.0534 AC: 817 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0499 AC: 173 AN: 3470

East Asian (EAS) AF: 0.000963 AC: 5 AN: 5190

South Asian (SAS) AF: 0.0158 AC: 76 AN: 4824

European-Finnish (FIN) AF: 0.0137 AC: 145 AN: 10612

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0544 AC: 3701 AN: 67992

Other (OTH) AF: 0.0620 AC: 131 AN: 2114

Alfa AF: 0.0596 Hom.: 54

Bravo AF: 0.0730

Asia WGS AF: 0.0180 AC: 63 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Jan 13, 2016

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

not provided Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

May 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Joubert syndrome Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Joubert syndrome 14 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.20		Position offset: -11

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs555284377; hg19: chr2-202492883;