Variant 9-99216461-CAAT-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2

The NM_033087.4(ALG2):c.*1470_*1472del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 437,218 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0029 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

ALG2
NM_033087.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.460

Variant links:

Genes affected

ALG2 (HGNC:23159): (ALG2 alpha-1,3/1,6-mannosyltransferase) This gene encodes a member of the glycosyltransferase 1 family. The encoded protein acts as an alpha 1,3 mannosyltransferase, mannosylating Man(2)GlcNAc(2)-dolichol diphosphate and Man(1)GlcNAc(2)-dolichol diphosphate to form Man(3)GlcNAc(2)-dolichol diphosphate. Defects in this gene have been associated with congenital disorder of glycosylation type Ih (CDG-Ii). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2008]

ALG2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00286 (436/152284) while in subpopulation AFR AF= 0.0102 (425/41542). AF 95% confidence interval is 0.00943. There are 3 homozygotes in gnomad4. There are 216 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
ALG2	NM_033087.4 linkuse as main transcript	c.1470_1472del	3_prime_UTR_variant	2/2	ENST00000476832.2	NP_149078.1
ALG2	XM_047423996.1 linkuse as main transcript	c.1470_1472del	3_prime_UTR_variant	2/2		XP_047279952.1
ALG2	NR_024532.2 linkuse as main transcript	n.2928_2930del	non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG2	ENST00000476832.2 linkuse as main transcript	c.1470_1472del		3_prime_UTR_variant	2/2	1	NM_033087.4	ENSP00000417764	P1	Q9H553-1
ALG2	ENST00000238477.5 linkuse as main transcript	c.2463_2465del		3_prime_UTR_variant, NMD_transcript_variant	3/3	2		ENSP00000432675

Frequencies

GnomAD3 genomes

AF:

0.00286

AC:

435

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0102

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000461

AC:

AN:

117016

Hom.:

AF XY:

0.000360

AC XY:

AN XY:

63852

show subpopulations

Gnomad AFR exome

AF:

0.00780

Gnomad AMR exome

AF:

0.000379

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000225

AC:

AN:

284934

Hom.:

AF XY:

0.000154

AC XY:

AN XY:

162206

show subpopulations

Gnomad4 AFR exome

AF:

0.00627

Gnomad4 AMR exome

AF:

0.000376

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:

0.0000132

Gnomad4 OTH exome

AF:

0.000377

GnomAD4 genome

AF:

0.00286

AC:

436

AN:

152284

Hom.:

Cov.:

AF XY:

0.00290

AC XY:

216

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0102

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00169

Hom.:

Bravo

AF:

0.00305

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Congenital disorder of glycosylation

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over