2-30966370-G-T

Variant names:

• chr2-30966370-G-T
• rs2303324
• NM_024572.4:c.300-68C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024572.4(GALNT14):​c.300-68C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000971 in 1,030,108 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 9.7e-7 (0 hom.)
• Consequence: GALNT14 NM_024572.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• Publications: 5 publications found

Genes affected

GALNT14 (HGNC:22946): (polypeptide N-acetylgalactosaminyltransferase 14) This gene encodes a Golgi protein which is a member of the polypeptide N-acetylgalactosaminyltransferase (ppGalNAc-Ts) protein family. These enzymes catalyze the transfer of N-acetyl-D-galactosamine (GalNAc) to the hydroxyl groups on serines and threonines in target peptides. The encoded protein has been shown to transfer GalNAc to large proteins like mucins. Alterations in this gene may play a role in cancer progression and response to chemotherapy. [provided by RefSeq, Jun 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024572.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT14	NM_024572.4	MANE Select	c.300-68C>A		intron	N/A	NP_078848.2	Q96FL9-1
	GALNT14	NM_001253826.2		c.315-68C>A		intron	N/A	NP_001240755.1	Q96FL9-3
	GALNT14	NM_001253827.2		c.240-68C>A		intron	N/A	NP_001240756.1	Q96FL9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT14	ENST00000349752.10	TSL:1 MANE Select	c.300-68C>A		intron	N/A	ENSP00000288988.6	Q96FL9-1
	GALNT14	ENST00000464038.5	TSL:1	n.559-68C>A		intron	N/A
	GALNT14	ENST00000324589.9	TSL:2	c.315-68C>A		intron	N/A	ENSP00000314500.5	Q96FL9-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.71e-7 AC: 1 AN: 1030108 Hom.: 0 AF XY: 0.00000190 AC XY: 1 AN XY: 527284

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25306

American (AMR) AF: 0.00 AC: 0 AN: 39684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22534

East Asian (EAS) AF: 0.00 AC: 0 AN: 36812

South Asian (SAS) AF: 0.00 AC: 0 AN: 73806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4888

European-Non Finnish (NFE) AF: 0.00000137 AC: 1 AN: 730038

Other (OTH) AF: 0.00 AC: 0 AN: 45846

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0090
DANN	Benign	0.31
PhyloP100		-2.0

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: rs2303324; hg19: chr2-31189236;