NM_173582.6:c.*14T>C

Variant names:

• chr11-74336638-A-G
• rs1044782
• NM_173582.6:c.*14T>C

Variant summary

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

The NM_173582.6(PGM2L1):​c.*14T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 1,554,914 control chromosomes in the GnomAD database, including 314,362 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (26527 hom., cov: 31)
  • Exomes 𝑓: 0.64 (287835 hom.)
• Consequence: PGM2L1 NM_173582.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.620
• Publications: 18 publications found

Genes affected

PGM2L1 (HGNC:20898): (phosphoglucomutase 2 like 1) Enables glucose-1,6-bisphosphate synthase activity. Predicted to be involved in glucose metabolic process and phosphorylation. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

PGM2L1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ENSG00000308977 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 11-74336638-A-G is Benign according to our data. Variant chr11-74336638-A-G is described in ClinVar as Benign. ClinVar VariationId is 1285855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173582.6. 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
	PGM2L1	NM_173582.6	MANE Select	c.*14T>C		3_prime_UTR	Exon 14 of 14	NP_775853.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGM2L1	ENST00000298198.5	TSL:1 MANE Select	c.*14T>C		3_prime_UTR	Exon 14 of 14	ENSP00000298198.4	Q6PCE3
	PGM2L1	ENST00000867622.1		c.*14T>C		3_prime_UTR	Exon 15 of 15	ENSP00000537681.1
	PGM2L1	ENST00000965981.1		c.*14T>C		3_prime_UTR	Exon 14 of 14	ENSP00000636040.1

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87935 AN: 151888 Hom.: 26515 Cov.: 31

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.803

Gnomad SAS AF: 0.662

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.572

GnomAD2 exomes AF: 0.643 AC: 153645 AN: 238998 AF XY: 0.642

Gnomad AFR exome AF: 0.401

Gnomad AMR exome AF: 0.682

Gnomad ASJ exome AF: 0.605

Gnomad EAS exome AF: 0.810

Gnomad FIN exome AF: 0.717

Gnomad NFE exome AF: 0.630

Gnomad OTH exome AF: 0.632

GnomAD4 exome AF: 0.638 AC: 894791 AN: 1402906 Hom.: 287835 Cov.: 24 AF XY: 0.638 AC XY: 446713 AN XY: 700274

African (AFR) AF: 0.387 AC: 12264 AN: 31674

American (AMR) AF: 0.678 AC: 27783 AN: 40996

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 15267 AN: 25210

East Asian (EAS) AF: 0.754 AC: 29539 AN: 39172

South Asian (SAS) AF: 0.641 AC: 52574 AN: 82060

European-Finnish (FIN) AF: 0.713 AC: 37821 AN: 53060

Middle Eastern (MID) AF: 0.567 AC: 3175 AN: 5604

European-Non Finnish (NFE) AF: 0.637 AC: 679576 AN: 1066856

Other (OTH) AF: 0.631 AC: 36792 AN: 58274

GnomAD4 genome AF: 0.579 AC: 87989 AN: 152008 Hom.: 26527 Cov.: 31 AF XY: 0.587 AC XY: 43624 AN XY: 74312

African (AFR) AF: 0.397 AC: 16456 AN: 41454

American (AMR) AF: 0.629 AC: 9603 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2087 AN: 3464

East Asian (EAS) AF: 0.802 AC: 4138 AN: 5158

South Asian (SAS) AF: 0.664 AC: 3195 AN: 4814

European-Finnish (FIN) AF: 0.716 AC: 7568 AN: 10566

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.631 AC: 42888 AN: 67968

Other (OTH) AF: 0.572 AC: 1209 AN: 2112

Alfa AF: 0.607 Hom.: 37695

Bravo AF: 0.565

Asia WGS AF: 0.691 AC: 2405 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.61
DANN	Benign	0.20
PhyloP100		-0.62
Mutation Taster		=100/0	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: rs1044782; hg19: chr11-74047683; COSMIC: COSV53346755;