chr1-183937480-G-A

Variant names:

• chr1-183937480-G-A
• rs2986574
• NM_015101.4:c.*1281C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015101.4(COLGALT2):​c.*1281C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 985,314 control chromosomes in the GnomAD database, including 17,835 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2310 hom., cov: 32)
  • Exomes 𝑓: 0.19 (15525 hom.)
• Consequence: COLGALT2 NM_015101.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• 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.*1281C>T		3_prime_UTR_variant	Exon 12 of 12	ENST00000361927.9	NP_055916.1
COLGALT2	NM_001303421.2	c.*1281C>T		3_prime_UTR_variant	Exon 12 of 12		NP_001290350.1
COLGALT2	NM_001303420.2	c.1604+3101C>T		intron_variant	Intron 11 of 11		NP_001290349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COLGALT2	ENST00000361927.9	c.*1281C>T		3_prime_UTR_variant	Exon 12 of 12	1	NM_015101.4	ENSP00000354960.4
COLGALT2	ENST00000367521.5	c.*1281C>T		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000356491.1
COLGALT2	ENST00000649786.1	c.1604+3101C>T		intron_variant	Intron 11 of 11			ENSP00000497601.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25238 AN: 152014 Hom.: 2309 Cov.: 32

Gnomad AFR AF: 0.0947

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: 0.189

GnomAD4 exome AF: 0.192 AC: 159571 AN: 833182 Hom.: 15525 Cov.: 36 AF XY: 0.192 AC XY: 73706 AN XY: 384752

African (AFR) AF: 0.0844 AC: 1333 AN: 15790

American (AMR) AF: 0.258 AC: 254 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 1042 AN: 5164

East Asian (EAS) AF: 0.198 AC: 719 AN: 3634

South Asian (SAS) AF: 0.231 AC: 3798 AN: 16462

European-Finnish (FIN) AF: 0.164 AC: 46 AN: 280

Middle Eastern (MID) AF: 0.209 AC: 339 AN: 1620

European-Non Finnish (NFE) AF: 0.193 AC: 146876 AN: 761950

Other (OTH) AF: 0.189 AC: 5164 AN: 27298

GnomAD4 genome AF: 0.166 AC: 25253 AN: 152132 Hom.: 2310 Cov.: 32 AF XY: 0.167 AC XY: 12425 AN XY: 74378

African (AFR) AF: 0.0947 AC: 3930 AN: 41506

American (AMR) AF: 0.252 AC: 3856 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 728 AN: 3466

East Asian (EAS) AF: 0.207 AC: 1074 AN: 5182

South Asian (SAS) AF: 0.227 AC: 1094 AN: 4810

European-Finnish (FIN) AF: 0.144 AC: 1519 AN: 10578

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

European-Non Finnish (NFE) AF: 0.185 AC: 12560 AN: 67990

Other (OTH) AF: 0.188 AC: 396 AN: 2112

Alfa AF: 0.174 Hom.: 874

Bravo AF: 0.173

Asia WGS AF: 0.210 AC: 726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.1
DANN	Benign	0.34
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2986574; hg19: chr1-183906614;