1-230067374-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_004481.5(GALNT2):c.94G>T(p.Ala32Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000866 in 1,154,718 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
• Consequence: GALNT2 NM_004481.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.61

Genes affected

GALNT2 (HGNC:4124): (polypeptide N-acetylgalactosaminyltransferase 2) This gene encodes a member of the glycosyltransferase 2 protein family. Members of this family initiate mucin-type O-glycoslation of peptides in the Golgi apparatus. The encoded protein may be involved in O-linked glycosylation of the immunoglobulin A1 hinge region. This gene may influence triglyceride levels, and may be involved Type 2 diabetes, as well as several types of cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19026566).
• BP6: Variant 1-230067374-G-T is Benign according to our data. Variant chr1-230067374-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3098160.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNT2	NM_004481.5	c.94G>T	p.Ala32Ser	missense_variant	1/16	ENST00000366672.5
GALNT2	NM_001291866.2	c.12+9296G>T		intron_variant
GALNT2	NR_120373.2	n.137G>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNT2	ENST00000366672.5	c.94G>T	p.Ala32Ser	missense_variant	1/16	1	NM_004481.5	P1
GALNT2	ENST00000488903.1	n.116G>T		non_coding_transcript_exon_variant	1/2	2
GALNT2	ENST00000494106.1	n.89+9296G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.66e-7 AC: 1 AN: 1154718 Hom.: 0 Cov.: 29 AF XY: 0.00000177 AC XY: 1 AN XY: 563684

Gnomad4 AFR exome AF: 0.00

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: 0.00000105

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 04, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
Cadd	Benign	21
Dann	Benign	0.83
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.40	T
M_CAP	Pathogenic	0.94	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.42	N
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.14	N
REVEL	Benign	0.10
Sift	Benign	0.52	T
Sift4G	Benign	0.74	T
Polyphen		0.0010	B
Vest4		0.18
MVP		0.45
MPC		0.49
ClinPred		0.089	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.040
gMVP		0.52

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: chr1-230203121;