7-75881904-G-C

Position:

• chr7-75881904-G-C

Variant summary

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

The NM_001040456.3(RHBDD2):​c.254G>C​(p.Arg85Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R85H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RHBDD2 NM_001040456.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.72

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 (HGNC:):

ACMG classification

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	c.254G>C	p.Arg85Pro	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	c.254G>C	p.Arg85Pro	missense_variant	2/4	1	NM_001040456.3	ENSP00000006777.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Benign	-0.000073	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	1.0	N
REVEL	Benign	0.23
Sift	Benign	0.33	T
Sift4G	Benign	0.20	T
Polyphen		0.99	D
Vest4		0.64
MutPred		0.53		Loss of helix (P = 0.0138);
MVP		0.24
MPC		1.1
ClinPred		0.83	D
GERP RS		3.8
Varity_R		0.18
gMVP		0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs11547498; hg19: chr7-75511222;