1-183938858-G-A

Position:

• chr1-183938858-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015101.4(COLGALT2):​c.1784C>T​(p.Ser595Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: COLGALT2 NM_015101.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.11

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3696711).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COLGALT2	NM_015101.4	c.1784C>T	p.Ser595Phe	missense_variant	12/12	ENST00000361927.9	NP_055916.1
COLGALT2	NM_001303421.2	c.1424C>T	p.Ser475Phe	missense_variant	12/12		NP_001290350.1
COLGALT2	NM_001303420.2	c.1604+1723C>T		intron_variant			NP_001290349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COLGALT2	ENST00000361927.9	c.1784C>T	p.Ser595Phe	missense_variant	12/12	1	NM_015101.4	ENSP00000354960.4
COLGALT2	ENST00000367520.3	c.995C>T	p.Ser332Phe	missense_variant	7/7	2		ENSP00000356490.3
COLGALT2	ENST00000367521.5	c.608C>T	p.Ser203Phe	missense_variant	4/4	2		ENSP00000356491.1
COLGALT2	ENST00000649786.1	c.1604+1723C>T		intron_variant				ENSP00000497601.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

Jun 22, 2024

The c.1784C>T (p.S595F) alteration is located in exon 12 (coding exon 12) of the COLGALT2 gene. This alteration results from a C to T substitution at nucleotide position 1784, causing the serine (S) at amino acid position 595 to be replaced by a phenylalanine (F). 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	0.29
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T;T;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Uncertain	-0.042	T
MutationAssessor	Benign	1.4	.;L;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Uncertain	0.39
Sift	Uncertain	0.0050	D;D;D
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		0.71, 0.58	.;P;P
Vest4		0.34
MutPred		0.33		.;Loss of disorder (P = 0.0117);.;
MVP		0.87
MPC		0.59
ClinPred		0.90	D
GERP RS		5.4
Varity_R		0.39
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-183907992;