rs1006328829

Variant names:

• chr2-73385935-G-GAGA
• rs1006328829
• NM_001378454.1:c.69_70insAAG

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP3

The ENST00000613296.6(ALMS1):​c.69_70insAAG​(p.Glu23_Glu24insLys) variant causes a conservative 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 (★). Synonymous variant affecting the same amino acid position (i.e. E24E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALMS1 ENST00000613296.6 conservative_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:3
• Conservation: PhyloP100: -0.190
• Publications: 0 publications found

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

ENSG00000285068 (HGNC:):

ACMG classification

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 ENST00000613296.6

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000613296.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALMS1	NM_001378454.1	MANE Select	c.69_70insAAG	p.Glu23_Glu24insLys	conservative_inframe_insertion	Exon 1 of 23	NP_001365383.1
	ALMS1	NM_015120.4		c.69_70insAAG	p.Glu23_Glu24insLys	conservative_inframe_insertion	Exon 1 of 23	NP_055935.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALMS1	ENST00000613296.6	TSL:1 MANE Select	c.69_70insAAG	p.Glu23_Glu24insLys	conservative_inframe_insertion	Exon 1 of 23	ENSP00000482968.1
	ALMS1	ENST00000484298.5	TSL:1	c.69_70insAAG	p.Glu23_Glu24insLys	conservative_inframe_insertion	Exon 1 of 22	ENSP00000478155.1
	ALMS1	ENST00000614410.4	TSL:5	c.69_70insAAG	p.Glu23_Glu24insLys	conservative_inframe_insertion	Exon 1 of 16	ENSP00000479094.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 13

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Asia WGS AF: 0.00116 AC: 4 AN: 3474

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	2	-	Alstrom syndrome (2)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.19

Splicing

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

Other links and lift over

dbSNP: rs1006328829; hg19: chr2-73613063;