15-23440775-C-CCCGCATCTTCTCCTCCTGCTTCCGCATCTTCTCCTCCTGCTT

Variant names:

• chr15-23440775-C-CCCGCATCTTCTCCTCCTGCTTCCGCATCTTCTCCTCCTGCTT
• rs748500078
• NM_001304388.2:c.1699_1700insAAGCAGGAGGAGAAGATGCGGAAGCAGGAGGAGAAGATGCGG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_001304388.2(GOLGA6L2):​c.1699_1700insAAGCAGGAGGAGAAGATGCGGAAGCAGGAGGAGAAGATGCGG​(p.Ala566_Gly567insGluAlaGlyGlyGluAspAlaGluAlaGlyGlyGluAspAla) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000155 in 1,287,448 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: GOLGA6L2 NM_001304388.2 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405
• Publications: 0 publications found

Genes affected

GOLGA6L2 (HGNC:26695): (golgin A6 family like 2) Predicted to be located in cis-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001304388.2.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304388.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA6L2	NM_001304388.2	MANE Select	c.1699_1700insAAGCAGGAGGAGAAGATGCGGAAGCAGGAGGAGAAGATGCGG	p.Ala566_Gly567insGluAlaGlyGlyGluAspAlaGluAlaGlyGlyGluAspAla	conservative_inframe_insertion	Exon 8 of 8	NP_001291317.1	Q8N9W4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA6L2	ENST00000567107.6	TSL:5 MANE Select	c.1699_1700insAAGCAGGAGGAGAAGATGCGGAAGCAGGAGGAGAAGATGCGG	p.Ala566_Gly567insGluAlaGlyGlyGluAspAlaGluAlaGlyGlyGluAspAla	conservative_inframe_insertion	Exon 8 of 8	ENSP00000454407.1	Q8N9W4-3
	GOLGA6L2	ENST00000566571.5	TSL:5	n.*980_*981insAAGCAGGAGGAGAAGATGCGGAAGCAGGAGGAGAAGATGCGG		non_coding_transcript_exon	Exon 7 of 7	ENSP00000456523.1	H3BS38
	GOLGA6L2	ENST00000566571.5	TSL:5	n.*980_*981insAAGCAGGAGGAGAAGATGCGGAAGCAGGAGGAGAAGATGCGG		3_prime_UTR	Exon 7 of 7	ENSP00000456523.1	H3BS38

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000155 AC: 2 AN: 1287448 Hom.: 0 Cov.: 98 AF XY: 0.00 AC XY: 0 AN XY: 638974

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29352

American (AMR) AF: 0.00 AC: 0 AN: 35400

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24384

East Asian (EAS) AF: 0.00 AC: 0 AN: 35026

South Asian (SAS) AF: 0.00 AC: 0 AN: 76830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42138

Middle Eastern (MID) AF: 0.000182 AC: 1 AN: 5496

European-Non Finnish (NFE) AF: 0.00000102 AC: 1 AN: 984472

Other (OTH) AF: 0.00 AC: 0 AN: 54350

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.41
Mutation Taster		=88/12	polymorphism

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs748500078; hg19: chr15-23685922;