rs2936818

Variant names:

• chr3-43081474-G-A
• rs2936818
• NM_032806.6:c.-43C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-43081474-G-A
• chr3-43081474-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032806.6(POMGNT2):​c.-43C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,460,022 control chromosomes in the GnomAD database, including 163,239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (14588 hom., cov: 33)
  • Exomes 𝑓: 0.47 (148651 hom.)
• Consequence: POMGNT2 NM_032806.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.605
• Publications: 6 publications found

Genes affected

POMGNT2 (HGNC:25902): (protein O-linked mannose N-acetylglucosaminyltransferase 2 (beta 1,4-)) This gene encodes a protein with glycosyltransferase activity although its function is not currently known. [provided by RefSeq, Sep 2012]

POMGNT2 Gene-Disease associations (from GenCC):

• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• myopathy caused by variation in POMGNT2

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• muscular dystrophy-dystroglycanopathy, type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-43081474-G-A is Benign according to our data. Variant chr3-43081474-G-A is described in ClinVar as Benign. ClinVar VariationId is 262102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032806.6. 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
	POMGNT2	NM_032806.6	MANE Select	c.-43C>T		5_prime_UTR	Exon 2 of 2	NP_116195.2
	POMGNT2	NM_001437285.1		c.-43C>T		5_prime_UTR	Exon 3 of 3	NP_001424214.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMGNT2	ENST00000344697.3	TSL:1 MANE Select	c.-43C>T		5_prime_UTR	Exon 2 of 2	ENSP00000344125.2
	POMGNT2	ENST00000441964.1	TSL:4	c.-43C>T		5_prime_UTR	Exon 3 of 3	ENSP00000408992.1
	POMGNT2	ENST00000686643.1		c.-43C>T		5_prime_UTR	Exon 4 of 4	ENSP00000509123.1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64548 AN: 151926 Hom.: 14578 Cov.: 33

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.456

GnomAD2 exomes AF: 0.491 AC: 50306 AN: 102478 AF XY: 0.492

Gnomad AFR exome AF: 0.265

Gnomad AMR exome AF: 0.619

Gnomad ASJ exome AF: 0.530

Gnomad EAS exome AF: 0.629

Gnomad FIN exome AF: 0.395

Gnomad NFE exome AF: 0.480

Gnomad OTH exome AF: 0.492

GnomAD4 exome AF: 0.474 AC: 619935 AN: 1307978 Hom.: 148651 Cov.: 24 AF XY: 0.474 AC XY: 302012 AN XY: 637480

African (AFR) AF: 0.266 AC: 7702 AN: 28916

American (AMR) AF: 0.599 AC: 14500 AN: 24190

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 9915 AN: 19366

East Asian (EAS) AF: 0.608 AC: 21741 AN: 35738

South Asian (SAS) AF: 0.456 AC: 30159 AN: 66092

European-Finnish (FIN) AF: 0.390 AC: 17114 AN: 43880

Middle Eastern (MID) AF: 0.483 AC: 2225 AN: 4604

European-Non Finnish (NFE) AF: 0.476 AC: 490725 AN: 1031034

Other (OTH) AF: 0.477 AC: 25854 AN: 54158

GnomAD4 genome AF: 0.425 AC: 64585 AN: 152044 Hom.: 14588 Cov.: 33 AF XY: 0.426 AC XY: 31692 AN XY: 74314

African (AFR) AF: 0.273 AC: 11313 AN: 41464

American (AMR) AF: 0.555 AC: 8489 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1771 AN: 3468

East Asian (EAS) AF: 0.623 AC: 3206 AN: 5142

South Asian (SAS) AF: 0.465 AC: 2235 AN: 4808

European-Finnish (FIN) AF: 0.388 AC: 4111 AN: 10598

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31897 AN: 67970

Other (OTH) AF: 0.453 AC: 956 AN: 2110

Alfa AF: 0.442 Hom.: 21791

Bravo AF: 0.434

Asia WGS AF: 0.520 AC: 1809 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 (1)
-	-	1	Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 8 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.8
DANN	Benign	0.78
PhyloP100		0.60
Mutation Taster		=300/0	polymorphism (auto)

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: rs2936818; hg19: chr3-43122966; COSMIC: COSV60953666;