rs121908582

Positions:

• chr2-169493765-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The ENST00000295240.8(BBS5):​c.547A>G​(p.Thr183Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BBS5 ENST00000295240.8 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.32

Genes affected

BBS5 (HGNC:970): (Bardet-Biedl syndrome 5) This gene encodes a protein that has been directly linked to Bardet-Biedl syndrome. The primary features of this syndrome include retinal dystrophy, obesity, polydactyly, renal abnormalities and learning disabilities. Experimentation in non-human eukaryotes suggests that this gene is expressed in ciliated cells and that it is required for the formation of cilia. Alternate transcriptional splice variants have been observed but have not been fully characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.926
• PP5: Variant 2-169493765-A-G is Pathogenic according to our data. Variant chr2-169493765-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 6162.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-169493765-A-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS5	NM_152384.3	c.547A>G	p.Thr183Ala	missense_variant	7/12	ENST00000295240.8	NP_689597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS5	ENST00000295240.8	c.547A>G	p.Thr183Ala	missense_variant	7/12	1	NM_152384.3	ENSP00000295240	P1
BBS5	ENST00000392663.6	c.547A>G	p.Thr183Ala	missense_variant	7/11	1		ENSP00000376431
BBS5	ENST00000443151.1	c.*269A>G		3_prime_UTR_variant, NMD_transcript_variant	5/6	5		ENSP00000406182

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Bardet-Biedl syndrome 5 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 15, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.72	D;.;.
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.92
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.93	D;D;D
MetaSVM	Uncertain	0.62	D
MutationAssessor	Pathogenic	2.9	M;M;.
MutationTaster	Benign	1.0	A;A;A
PROVEAN	Uncertain	-4.3	D;D;D
REVEL	Pathogenic	0.84
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.0060	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.87
MutPred		0.80		Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);
MVP		0.96
MPC		1.1
ClinPred		0.99	D
GERP RS		6.0
Varity_R		0.45
gMVP		0.78

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: rs121908582; hg19: chr2-170350275;