Genetic Variant ALMS1:p.Glu26_Glu27dup (chr2-73385937-G-GGAGGAA) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3

The NM_001378454.1(ALMS1):c.75_80dupAGAGGA(p.Glu26_Glu27dup) variant causes a disruptive inframe insertion 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 Uncertain significance (★★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ALMS1
NM_001378454.1 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.251

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, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ALMS1 links:

ENSG00000285068 (HGNC:):

ENSG00000285068 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP3

Nonframeshift variant in repetitive region in NM_001378454.1

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378454.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALMS1	NM_001378454.1	MANE Select	c.75_80dupAGAGGA	p.Glu26_Glu27dup	disruptive_inframe_insertion	Exon 1 of 23	NP_001365383.1	Q8TCU4-1
	ALMS1	NM_015120.4		c.75_80dupAGAGGA	p.Glu26_Glu27dup	disruptive_inframe_insertion	Exon 1 of 23	NP_055935.4	Q8TCU4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALMS1	ENST00000613296.6	TSL:1 MANE Select	c.75_80dupAGAGGA	p.Glu26_Glu27dup	disruptive_inframe_insertion	Exon 1 of 23	ENSP00000482968.1	Q8TCU4-1
ALMS1	ENST00000484298.5	TSL:1	c.75_80dupAGAGGA	p.Glu26_Glu27dup	disruptive_inframe_insertion	Exon 1 of 22	ENSP00000478155.1	A0A087WTU9
ALMS1	ENST00000614410.4	TSL:5	c.75_80dupAGAGGA	p.Glu26_Glu27dup	disruptive_inframe_insertion	Exon 1 of 16	ENSP00000479094.1	A0A087WV20

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

869316

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

444022

African (AFR)

AF:

0.00

AC:

AN:

16878

American (AMR)

AF:

0.00

AC:

AN:

30770

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20064

East Asian (EAS)

AF:

0.00

AC:

AN:

33064

South Asian (SAS)

AF:

0.00

AC:

AN:

63912

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45986

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3886

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

614646

Other (OTH)

AF:

0.00

AC:

AN:

40110

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

ALMS1-related disorder (1)

Alstrom syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.25

Splicing

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

Publications

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2-73385937-GGAGGAA-GGAGGAAGAGGAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over