rs748500078

Variant names:

• chr15-23440775-C-CCCGCATCTTCTCCTCCTGCTT
• rs748500078
• NM_001304388.2:c.1699_1700insAAGCAGGAGGAGAAGATGCGG

Your query was ambiguous. Multiple possible variants found:

• chr15-23440775-C-CCCGCATCTTCTCCTCCTGCTT
• chr15-23440775-C-CCCGCATCTTCTCCTCCTGCTA
• chr15-23440775-C-CCCGCATCTTCTCCTCCTGCTG
• chr15-23440775-C-CCCGCATCTTCTCCTCCTGCTTCCGCATCTTCTCCTCCTGCTT

Variant summary

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

The NM_001304388.2(GOLGA6L2):​c.1699_1700insAAGCAGGAGGAGAAGATGCGG​(p.Ala566_Gly567insGluAlaGlyGlyGluAspAla) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.47 (1 hom., cov: 0)
  • Exomes 𝑓: 0.45 (49 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6L2 NM_001304388.2 conservative_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: -0.405
• Publications: 3 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_1700insAAGCAGGAGGAGAAGATGCGG	p.Ala566_Gly567insGluAlaGlyGlyGluAspAla	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_1700insAAGCAGGAGGAGAAGATGCGG	p.Ala566_Gly567insGluAlaGlyGlyGluAspAla	conservative_inframe_insertion	Exon 8 of 8	ENSP00000454407.1	Q8N9W4-3
	GOLGA6L2	ENST00000566571.5	TSL:5	n.*980_*981insAAGCAGGAGGAGAAGATGCGG		non_coding_transcript_exon	Exon 7 of 7	ENSP00000456523.1	H3BS38
	GOLGA6L2	ENST00000566571.5	TSL:5	n.*980_*981insAAGCAGGAGGAGAAGATGCGG		3_prime_UTR	Exon 7 of 7	ENSP00000456523.1	H3BS38

Frequencies

GnomAD3 genomes AF: 0.472 AC: 66768 AN: 141536 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.486

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.483

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.446 AC: 423941 AN: 950718 Hom.: 49 Cov.: 98 AF XY: 0.450 AC XY: 216152 AN XY: 480832

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

African (AFR) AF: 0.373 AC: 8249 AN: 22136

American (AMR) AF: 0.482 AC: 15624 AN: 32418

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 9962 AN: 21140

East Asian (EAS) AF: 0.480 AC: 15631 AN: 32556

South Asian (SAS) AF: 0.468 AC: 31209 AN: 66644

European-Finnish (FIN) AF: 0.488 AC: 19856 AN: 40712

Middle Eastern (MID) AF: 0.468 AC: 2222 AN: 4744

European-Non Finnish (NFE) AF: 0.439 AC: 301630 AN: 687314

Other (OTH) AF: 0.454 AC: 19558 AN: 43054

⚠️ 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 Data not reliable, filtered out with message: InbreedingCoeff AF: 0.472 AC: 66815 AN: 141648 Hom.: 1 Cov.: 0 AF XY: 0.471 AC XY: 32748 AN XY: 69464

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

African (AFR) AF: 0.426 AC: 15860 AN: 37210

American (AMR) AF: 0.487 AC: 7076 AN: 14520

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1604 AN: 3294

East Asian (EAS) AF: 0.484 AC: 2269 AN: 4686

South Asian (SAS) AF: 0.480 AC: 2145 AN: 4470

European-Finnish (FIN) AF: 0.492 AC: 4976 AN: 10110

Middle Eastern (MID) AF: 0.489 AC: 134 AN: 274

European-Non Finnish (NFE) AF: 0.488 AC: 31378 AN: 64266

Other (OTH) AF: 0.485 AC: 948 AN: 1956

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.172 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)

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

Other links and lift over

dbSNP: rs748500078; hg19: chr15-23685922; COSMIC: COSV61485127;