chr1-183938790-C-T

Position:

• chr1-183938790-C-T

Variant summary

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

The NM_015101.4(COLGALT2):​c.1852G>A​(p.Asp618Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: COLGALT2 NM_015101.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.73

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]

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=0.19444242).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COLGALT2	NM_015101.4	c.1852G>A	p.Asp618Asn	missense_variant	12/12	ENST00000361927.9
COLGALT2	NM_001303421.2	c.1492G>A	p.Asp498Asn	missense_variant	12/12
COLGALT2	NM_001303420.2	c.1604+1791G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COLGALT2	ENST00000361927.9	c.1852G>A	p.Asp618Asn	missense_variant	12/12	1	NM_015101.4	P1
COLGALT2	ENST00000367520.3	c.1063G>A	p.Asp355Asn	missense_variant	7/7	2
COLGALT2	ENST00000367521.5	c.676G>A	p.Asp226Asn	missense_variant	4/4	2
COLGALT2	ENST00000649786.1	c.1604+1791G>A		intron_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461868 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727234

Gnomad4 AFR exome AF: 0.000119

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 09, 2021

The c.1852G>A (p.D618N) alteration is located in exon 12 (coding exon 12) of the COLGALT2 gene. This alteration results from a G to A substitution at nucleotide position 1852, causing the aspartic acid (D) at amino acid position 618 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T;T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.066
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.73	T;T;T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-0.52	T
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Uncertain	0.32
Sift	Benign	0.054	T;D;D
Sift4G	Benign	0.18	T;T;T
Polyphen		0.0030, 0.0010	.;B;B
Vest4		0.18
MutPred		0.13		.;Loss of phosphorylation at T615 (P = 0.1168);.;
MVP		0.81
MPC		0.30
ClinPred		0.51	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.097
gMVP		0.38

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: rs772199060; hg19: chr1-183907924;