rs2296713

Variant names:

• chr1-183940583-G-A
• rs2296713
• NM_015101.4:c.1602C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_015101.4(COLGALT2):​c.1602C>T​(p.Pro534Pro) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,613,722 control chromosomes in the GnomAD database, including 31,215 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2308 hom., cov: 32)
  • Exomes 𝑓: 0.19 (28907 hom.)
• Consequence: COLGALT2 NM_015101.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.03064
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• Publications: 18 publications found

Genes affected

COLGALT2 (HGNC:16790): (collagen beta(1-O)galactosyltransferase 2) Predicted to enable procollagen galactosyltransferase activity. Predicted to be involved in collagen fibril organization. Predicted to be located in endoplasmic reticulum lumen. [provided by Alliance of Genome Resources, Apr 2022]

COLGALT2 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=-0.042 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COLGALT2	NM_015101.4	c.1602C>T	p.Pro534Pro	splice_region_variant, synonymous_variant	Exon 11 of 12	ENST00000361927.9	NP_055916.1
COLGALT2	NM_001303420.2	c.1602C>T	p.Pro534Pro	splice_region_variant, synonymous_variant	Exon 11 of 12		NP_001290349.1
COLGALT2	NM_001303421.2	c.1242C>T	p.Pro414Pro	splice_region_variant, synonymous_variant	Exon 11 of 12		NP_001290350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COLGALT2	ENST00000361927.9	c.1602C>T	p.Pro534Pro	splice_region_variant, synonymous_variant	Exon 11 of 12	1	NM_015101.4	ENSP00000354960.4
COLGALT2	ENST00000649786.1	c.1602C>T	p.Pro534Pro	splice_region_variant, synonymous_variant	Exon 11 of 12			ENSP00000497601.1
COLGALT2	ENST00000367520.3	c.813C>T	p.Pro271Pro	splice_region_variant, synonymous_variant	Exon 6 of 7	2		ENSP00000356490.3
COLGALT2	ENST00000367521.5	c.426C>T	p.Pro142Pro	splice_region_variant, synonymous_variant	Exon 3 of 4	2		ENSP00000356491.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25165 AN: 152090 Hom.: 2307 Cov.: 32

Gnomad AFR AF: 0.0918

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.188

GnomAD2 exomes AF: 0.202 AC: 50811 AN: 251430 AF XY: 0.202

Gnomad AFR exome AF: 0.0869

Gnomad AMR exome AF: 0.308

Gnomad ASJ exome AF: 0.203

Gnomad EAS exome AF: 0.207

Gnomad FIN exome AF: 0.146

Gnomad NFE exome AF: 0.188

Gnomad OTH exome AF: 0.204

GnomAD4 exome AF: 0.194 AC: 284194 AN: 1461514 Hom.: 28907 Cov.: 33 AF XY: 0.195 AC XY: 142143 AN XY: 727096

African (AFR) AF: 0.0850 AC: 2847 AN: 33476

American (AMR) AF: 0.298 AC: 13334 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 5281 AN: 26134

East Asian (EAS) AF: 0.246 AC: 9770 AN: 39694

South Asian (SAS) AF: 0.232 AC: 19999 AN: 86244

European-Finnish (FIN) AF: 0.151 AC: 8081 AN: 53420

Middle Eastern (MID) AF: 0.227 AC: 1305 AN: 5744

European-Non Finnish (NFE) AF: 0.191 AC: 212130 AN: 1111724

Other (OTH) AF: 0.190 AC: 11447 AN: 60356

GnomAD4 genome AF: 0.165 AC: 25181 AN: 152208 Hom.: 2308 Cov.: 32 AF XY: 0.167 AC XY: 12402 AN XY: 74420

African (AFR) AF: 0.0918 AC: 3814 AN: 41528

American (AMR) AF: 0.253 AC: 3863 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 729 AN: 3472

East Asian (EAS) AF: 0.207 AC: 1070 AN: 5174

South Asian (SAS) AF: 0.227 AC: 1095 AN: 4814

European-Finnish (FIN) AF: 0.144 AC: 1527 AN: 10600

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12592 AN: 68018

Other (OTH) AF: 0.187 AC: 395 AN: 2112

Alfa AF: 0.187 Hom.: 12023

Bravo AF: 0.172

Asia WGS AF: 0.209 AC: 724 AN: 3478

EpiCase AF: 0.196

EpiControl AF: 0.201

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	4.8
DANN	Benign	0.70
PhyloP100		-0.042
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.031
dbscSNV1_RF	Benign	0.24
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2296713; hg19: chr1-183909717; COSMIC: COSV62299337;