chr15-23440775-C-T

Position:

• chr15-23440775-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001304388.2(GOLGA6L2):​c.1700G>A​(p.Gly567Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000362 in 1,437,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 35)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: GOLGA6L2 NM_001304388.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.480

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09551898).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GOLGA6L2	NM_001304388.2	c.1700G>A	p.Gly567Glu	missense_variant	8/8	ENST00000567107.6
GOLGA6L2	XM_047432396.1	c.1541G>A	p.Gly514Glu	missense_variant	6/6
GOLGA6L2	XM_047432397.1	c.1228-249G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GOLGA6L2	ENST00000567107.6	c.1700G>A	p.Gly567Glu	missense_variant	8/8	5	NM_001304388.2	P1
GOLGA6L2	ENST00000566571.5	c.*981G>A		3_prime_UTR_variant, NMD_transcript_variant	7/7	5

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 2 AN: 149948 Hom.: 0 Cov.: 35

Gnomad AFR AF: 0.0000248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000660

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000388 AC: 50 AN: 1287412 Hom.: 0 Cov.: 44 AF XY: 0.0000376 AC XY: 24 AN XY: 638958

Gnomad4 AFR exome AF: 0.0000341

Gnomad4 AMR exome AF: 0.0000565

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000286

Gnomad4 SAS exome AF: 0.0000390

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000427

Gnomad4 OTH exome AF: 0.0000184

GnomAD4 genome AF: 0.0000133 AC: 2 AN: 149948 Hom.: 0 Cov.: 35 AF XY: 0.0000273 AC XY: 2 AN XY: 73226

Gnomad4 AFR AF: 0.0000248

Gnomad4 AMR AF: 0.0000660

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.102 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	6.2
DANN	Benign	0.65
FATHMM_MKL	Benign	0.00061	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.096	T
MutationTaster	Benign	1.0	N;N;N
PROVEAN	Benign	1.1	N
Sift4G	Benign	0.077	T
Vest4		0.11
MVP		0.48
MPC		0.014
Varity_R		0.092
gMVP		0.042

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs377626801; hg19: chr15-23685922; COSMIC: COSV61472904;