rs2075827

Variant names:

• chr16-8847961-A-C
• rs2075827
• NM_000303.3:c.*136A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-8847961-A-C
• chr16-8847961-A-T

Variant summary

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

The NM_000303.3(PMM2):​c.*136A>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 0.265 in 668,580 control chromosomes in the GnomAD database, including 24,247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (4994 hom., cov: 33)
  • Exomes 𝑓: 0.27 (19253 hom.)
• Consequence: PMM2 NM_000303.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0670
• Publications: 14 publications found

Genes affected

PMM2 (HGNC:9115): (phosphomannomutase 2) The protein encoded by this gene catalyzes the isomerization of mannose 6-phosphate to mannose 1-phosphate, which is a precursor to GDP-mannose necessary for the synthesis of dolichol-P-oligosaccharides. Mutations in this gene have been shown to cause defects in glycoprotein biosynthesis, which manifests as carbohydrate-deficient glycoprotein syndrome type I. [provided by RefSeq, Jul 2008]

PMM2 Gene-Disease associations (from GenCC):

• congenital disorder of glycosylation type I

  Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
• PMM2-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• hyperinsulinemic hypoglycemia with polycystic kidney disease

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ENSG00000260350 (HGNC:58482):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-8847961-A-C is Benign according to our data. Variant chr16-8847961-A-C is described in ClinVar as Benign. ClinVar VariationId is 321229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000303.3. 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
	PMM2	NM_000303.3	MANE Select	c.*136A>C		3_prime_UTR	Exon 8 of 8	NP_000294.1	A0A0S2Z4J6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMM2	ENST00000268261.9	TSL:1 MANE Select	c.*136A>C		3_prime_UTR	Exon 8 of 8	ENSP00000268261.4	O15305-1
	PMM2	ENST00000565221.5	TSL:1	n.*495A>C		non_coding_transcript_exon	Exon 6 of 6	ENSP00000457932.1	H3BV34
	PMM2	ENST00000566540.5	TSL:1	n.*499A>C		non_coding_transcript_exon	Exon 6 of 6	ENSP00000454284.1	H3BM92

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38450 AN: 152032 Hom.: 4994 Cov.: 33

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.245

GnomAD4 exome AF: 0.268 AC: 138660 AN: 516430 Hom.: 19253 Cov.: 6 AF XY: 0.273 AC XY: 75198 AN XY: 275032

African (AFR) AF: 0.222 AC: 3327 AN: 14984

American (AMR) AF: 0.185 AC: 5683 AN: 30770

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 3723 AN: 16924

East Asian (EAS) AF: 0.310 AC: 9735 AN: 31406

South Asian (SAS) AF: 0.337 AC: 18986 AN: 56282

European-Finnish (FIN) AF: 0.284 AC: 9162 AN: 32264

Middle Eastern (MID) AF: 0.237 AC: 541 AN: 2282

European-Non Finnish (NFE) AF: 0.264 AC: 80050 AN: 302828

Other (OTH) AF: 0.260 AC: 7453 AN: 28690

GnomAD4 genome AF: 0.253 AC: 38456 AN: 152150 Hom.: 4994 Cov.: 33 AF XY: 0.256 AC XY: 19070 AN XY: 74392

African (AFR) AF: 0.220 AC: 9135 AN: 41508

American (AMR) AF: 0.214 AC: 3269 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 774 AN: 3468

East Asian (EAS) AF: 0.320 AC: 1658 AN: 5174

South Asian (SAS) AF: 0.340 AC: 1639 AN: 4822

European-Finnish (FIN) AF: 0.298 AC: 3163 AN: 10598

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 18018 AN: 67976

Other (OTH) AF: 0.247 AC: 523 AN: 2116

Alfa AF: 0.258 Hom.: 21613

Bravo AF: 0.240

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	PMM2-congenital disorder of glycosylation (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.53
PhyloP100		-0.067
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: rs2075827; hg19: chr16-8941818;