Variant 7-75882192-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000006777.11(RHBDD2):c.542C>T(p.Thr181Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,746 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RHBDD2
ENST00000006777.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.23

Variant links:

Genes affected

RHBDD2 (HGNC:23082): (rhomboid domain containing 2) The protein encoded by this gene is a member of the rhomboid family of membrane-bound proteases and is overexpressed in some breast cancers. Members of this family are involved in intramembrane proteolysis. In mouse, the orthologous protein associates with the Golgi body. [provided by RefSeq, Sep 2016]

RHBDD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHBDD2	NM_001040456.3 linkuse as main transcript	c.542C>T	p.Thr181Ile	missense_variant	2/4	ENST00000006777.11	NP_001035546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHBDD2	ENST00000006777.11 linkuse as main transcript	c.542C>T	p.Thr181Ile	missense_variant	2/4	1	NM_001040456.3	ENSP00000006777	P1	Q6NTF9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000804

AC:

AN:

248862

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135044

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461746

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2024

The c.542C>T (p.T181I) alteration is located in exon 2 (coding exon 2) of the RHBDD2 gene. This alteration results from a C to T substitution at nucleotide position 542, causing the threonine (T) at amino acid position 181 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.048

T;.;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.84

T;T;.

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;.;.

MutationTaster

Benign

0.96

D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.4

N;D;D

REVEL

Benign

0.18

Sift

Uncertain

0.010

D;D;D

Sift4G

Uncertain

0.023

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.62

MutPred

0.54

Gain of helix (P = 0.062);.;.;

MVP

0.20

MPC

0.98

ClinPred

0.72

GERP RS

5.5

Varity_R

0.16

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over