rs2107703319

Variant names:

• chr3-119469123-GCCGAGCCTGCCCCTTGGGCTCGGGGTCTGGCCGGAGTCCCGAGGCGCTCC-G
• rs2107703319
• NM_152305.3:c.85+20_85+69delGAGCCTGCCCCTTGGGCTCGGGGTCTGGCCGGAGTCCCGAGGCGCTCCCC

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_152305.3(POGLUT1):​c.85+20_85+69delGAGCCTGCCCCTTGGGCTCGGGGTCTGGCCGGAGTCCCGAGGCGCTCCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: POGLUT1 NM_152305.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.49
• Publications: 0 publications found

Genes affected

POGLUT1 (HGNC:22954): (protein O-glucosyltransferase 1) This gene encodes a protein with both O-glucosyltransferase and O-xylosyltransferase activity which localizes to the lumen of the endoplasmic reticulum. This protein has a carboxy-terminal KTEL motif which is predicted to function as an endoplasmic reticulum retention signal. This gene is an essential regulator of Notch signalling and likely plays a role in cell fate and tissue formation during development. It may also play a role in the pathogenesis of leukemia. Mutations in this gene have been associated with the autosomal dominant genodermatosis Dowling-Degos disease 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]

POGLUT1 Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Dowling-Degos disease 4

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• autosomal recessive limb-girdle muscular dystrophy type 2R1

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Dowling-Degos disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 3-119469123-GCCGAGCCTGCCCCTTGGGCTCGGGGTCTGGCCGGAGTCCCGAGGCGCTCC-G is Benign according to our data. Variant chr3-119469123-GCCGAGCCTGCCCCTTGGGCTCGGGGTCTGGCCGGAGTCCCGAGGCGCTCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 1645031.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POGLUT1	NM_152305.3	c.85+20_85+69delGAGCCTGCCCCTTGGGCTCGGGGTCTGGCCGGAGTCCCGAGGCGCTCCCC		intron_variant	Intron 1 of 10	ENST00000295588.9	NP_689518.1
POGLUT1	NR_024265.2	n.144+20_144+69delGAGCCTGCCCCTTGGGCTCGGGGTCTGGCCGGAGTCCCGAGGCGCTCCCC		intron_variant	Intron 1 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POGLUT1	ENST00000295588.9	c.85+20_85+69delGAGCCTGCCCCTTGGGCTCGGGGTCTGGCCGGAGTCCCGAGGCGCTCCCC		intron_variant	Intron 1 of 10	1	NM_152305.3	ENSP00000295588.4

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5

Splicing

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

Other links and lift over

dbSNP: rs2107703319; hg19: chr3-119187970;