chr2-73385823-T-TCCC

Position:

• chr2-73385823-T-TCCC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The ENST00000484298.5(ALMS1):​c.-41_-39dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000608 in 658,298 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000039 (0 hom.)
• Consequence: ALMS1 ENST00000484298.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.98

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 2-73385823-T-TCCC is Benign according to our data. Variant chr2-73385823-T-TCCC is described in ClinVar as [Likely_benign]. Clinvar id is 1181312.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALMS1	NM_015120.4	c.-41_-39dup		5_prime_UTR_variant	1/23		NP_055935.4
ALMS1	NM_001378454.1			upstream_gene_variant		ENST00000613296.6	NP_001365383.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALMS1	ENST00000484298.5	c.-41_-39dup		5_prime_UTR_variant	1/22	1		ENSP00000478155	A2
ALMS1	ENST00000613296.6			upstream_gene_variant		1	NM_001378454.1	ENSP00000482968	P3
ALMS1	ENST00000614410.4			upstream_gene_variant		5		ENSP00000479094

Frequencies

GnomAD3 genomes AF: 0.0000138 AC: 2 AN: 144946 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000390 AC: 2 AN: 513352 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 276164

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000675

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000138 AC: 2 AN: 144946 Hom.: 0 Cov.: 32 AF XY: 0.0000142 AC XY: 1 AN XY: 70374

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 27, 2017

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs764473588; hg19: chr2-73612951;