Genetic Variant ALMS1:c.-11_-2delGAGACACCAA (chr2-73385857-CGAGACACCAA-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_001378454.1(ALMS1):c.-11_-2delGAGACACCAA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ALMS1
NM_001378454.1 5_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.10

Publications

0 publications found

Variant links:

Genes affected

ALMS1 (HGNC:428): (ALMS1 centrosome and basal body associated protein) This gene encodes a protein containing a large tandem-repeat domain as well as additional low complexity regions. The encoded protein functions in microtubule organization, particularly in the formation and maintanance of cilia. Mutations in this gene cause Alstrom syndrome. There is a pseudogene for this gene located adjacent in the same region of chromosome 2. Alternative splice variants have been described but their full length nature has not been determined. [provided by RefSeq, Apr 2014]

ALMS1 Gene-Disease associations (from GenCC):

Alstrom syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, G2P, Orphanet, Genomics England PanelApp

ALMS1 links:

ENSG00000285068 (HGNC:):

ENSG00000285068 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 2-73385857-CGAGACACCAA-C is Benign according to our data. Variant chr2-73385857-CGAGACACCAA-C is described in ClinVar as [Likely_benign]. Clinvar id is 1792180.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ALMS1	NM_001378454.1 link	c.-11_-2delGAGACACCAA	5_prime_UTR_variant	Exon 1 of 23	ENST00000613296.6	NP_001365383.1
ALMS1	NM_015120.4 link	c.-11_-2delGAGACACCAA	5_prime_UTR_variant	Exon 1 of 23		NP_055935.4	Q8TCU4
LOC105374804	XR_007087045.1 link	n.-186_-177delTTGGTGTCTC	upstream_gene_variant
LOC105374804	XR_007087053.1 link	n.-186_-177delTTGGTGTCTC	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALMS1	ENST00000613296.6 link	c.-11_-2delGAGACACCAA		5_prime_UTR_variant	Exon 1 of 23	1	NM_001378454.1	ENSP00000482968.1		Q8TCU4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

575468

Hom.:

AF XY:

0.00

AC XY:

AN XY:

309748

African (AFR)

AF:

0.00

AC:

AN:

16062

American (AMR)

AF:

0.00

AC:

AN:

34424

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19944

East Asian (EAS)

AF:

0.00

AC:

AN:

31966

South Asian (SAS)

AF:

0.00

AC:

AN:

62186

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37660

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2502

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

339540

Other (OTH)

AF:

0.00

AC:

AN:

31184

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cardiovascular phenotype

Benign:1

Aug 04, 2020

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.1

Mutation Taster

=297/3

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over