2-73385828-C-CCCT

Position:

• chr2-73385828-C-CCCT

Variant summary

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

The ENST00000484298.5(ALMS1):​c.-27_-25dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000977 in 665,138 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000086 (0 hom.)
• Consequence: ALMS1 ENST00000484298.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.530

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 2-73385828-C-CCCT is Benign according to our data. Variant chr2-73385828-C-CCCT is described in ClinVar as [Benign]. Clinvar id is 421812.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.-27_-25dup		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.-27_-25dup		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: 0.000138 AC: 21 AN: 151666 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000885

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000157 AC: 11 AN: 69986 Hom.: 0 AF XY: 0.000240 AC XY: 9 AN XY: 37562

Gnomad AFR exome AF: 0.000664

Gnomad AMR exome AF: 0.000283

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000348

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000393

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000857 AC: 44 AN: 513370 Hom.: 0 Cov.: 0 AF XY: 0.000101 AC XY: 28 AN XY: 276450

Gnomad4 AFR exome AF: 0.000279

Gnomad4 AMR exome AF: 0.000279

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000333

Gnomad4 SAS exome AF: 0.000196

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000535

Gnomad4 OTH exome AF: 0.000105

GnomAD4 genome AF: 0.000138 AC: 21 AN: 151768 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74178

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000885

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 05, 2019

- -

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: rs746980000; hg19: chr2-73612956;