Genetic Variant NM_004481.5:c.72C>T (chr1-230067352-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_004481.5(GALNT2):c.72C>T(p.Tyr24Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000291 in 1,372,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000025 ( 0 hom. )

Consequence

GALNT2
NM_004481.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.04

Publications

0 publications found

Variant links:

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]

GALNT2 Gene-Disease associations (from GenCC):

congenital disorder of glycosylation, type iit
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

GALNT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 1-230067352-C-T is Benign according to our data. Variant chr1-230067352-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1925703.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.04 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004481.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GALNT2	NM_004481.5	MANE Select	c.72C>T	p.Tyr24Tyr	synonymous	Exon 1 of 16	NP_004472.1	A0A1L7NY50
GALNT2	NM_001291866.2		c.12+9274C>T		intron	N/A	NP_001278795.1
GALNT2	NR_120373.2		n.115C>T		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GALNT2	ENST00000366672.5	TSL:1 MANE Select	c.72C>T	p.Tyr24Tyr	synonymous	Exon 1 of 16	ENSP00000355632.4	Q10471-1
GALNT2	ENST00000935982.1		c.72C>T	p.Tyr24Tyr	synonymous	Exon 1 of 16	ENSP00000606041.1
GALNT2	ENST00000950855.1		c.72C>T	p.Tyr24Tyr	synonymous	Exon 1 of 16	ENSP00000620914.1

Frequencies

GnomAD3 genomes

AF:

0.00000667

AC:

AN:

149900

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000662

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000998

AC:

AN:

100224

AF XY:

0.0000173

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000235

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000245

AC:

AN:

1222376

Hom.:

Cov.:

AF XY:

0.00000498

AC XY:

AN XY:

602498

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24652

American (AMR)

AF:

0.00

AC:

AN:

21848

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19108

East Asian (EAS)

AF:

0.00

AC:

AN:

25502

South Asian (SAS)

AF:

0.0000180

AC:

AN:

55494

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40802

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4436

European-Non Finnish (NFE)

AF:

0.00000203

AC:

AN:

983134

Other (OTH)

AF:

0.00

AC:

AN:

47400

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000667

AC:

AN:

149900

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73088

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41068

American (AMR)

AF:

0.0000662

AC:

AN:

15110

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3430

East Asian (EAS)

AF:

0.00

AC:

AN:

5084

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9932

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67188

Other (OTH)

AF:

0.00

AC:

AN:

2054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.98

PhyloP100

1.0

PromoterAI

-0.033

Neutral

(source)

Mutation Taster

=265/35

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over