rs2282245

Variant names:

• chr9-21815798-C-T
• rs2282245
• NM_002451.4:c.120+279C>T

Variant summary

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

The NM_002451.4(MTAP):​c.120+279C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,026 control chromosomes in the GnomAD database, including 2,981 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.18 (2981 hom., cov: 31)
• Consequence: MTAP NM_002451.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.52
• Publications: 3 publications found

Genes affected

MTAP (HGNC:7413): (methylthioadenosine phosphorylase) This gene encodes an enzyme that plays a major role in polyamine metabolism and is important for the salvage pathway of both adenine and methionine. The encoded enzyme is deficient in many cancers. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Sep 2021]

MTAP Gene-Disease associations (from GenCC):

• diaphyseal medullary stenosis-bone malignancy syndrome

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Genomics England PanelApp, G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000264545 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 9-21815798-C-T is Benign according to our data. Variant chr9-21815798-C-T is described in ClinVar as [Benign]. Clinvar id is 1238889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTAP	NM_002451.4	c.120+279C>T		intron_variant	Intron 2 of 7	ENST00000644715.2	NP_002442.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTAP	ENST00000644715.2	c.120+279C>T		intron_variant	Intron 2 of 7		NM_002451.4	ENSP00000494373.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27016 AN: 151908 Hom.: 2980 Cov.: 31

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.170

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.178 AC: 27039 AN: 152026 Hom.: 2981 Cov.: 31 AF XY: 0.177 AC XY: 13189 AN XY: 74322

African (AFR) AF: 0.299 AC: 12392 AN: 41420

American (AMR) AF: 0.180 AC: 2743 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 552 AN: 3462

East Asian (EAS) AF: 0.264 AC: 1364 AN: 5158

South Asian (SAS) AF: 0.161 AC: 775 AN: 4818

European-Finnish (FIN) AF: 0.121 AC: 1280 AN: 10578

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7220 AN: 68014

Other (OTH) AF: 0.168 AC: 355 AN: 2110

Alfa AF: 0.128 Hom.: 789

Bravo AF: 0.192

Asia WGS AF: 0.233 AC: 809 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.065
DANN	Benign	0.28
PhyloP100		-1.5
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: rs2282245; hg19: chr9-21815797;