rs2165408

Variant names:

• chr9-21802470-A-G
• rs2165408
• NM_002451.4:c.-279A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-21802470-A-G
• chr9-21802470-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002451.4(MTAP):​c.-279A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 337,078 control chromosomes in the GnomAD database, including 19,376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (17329 hom., cov: 23)
  • Exomes 𝑓: 0.50 (2047 hom.)
• Consequence: MTAP NM_002451.4 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.155

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]

ENSG00000264545 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 9-21802470-A-G is Benign according to our data. Variant chr9-21802470-A-G is described in ClinVar as [Benign]. Clinvar id is 1228035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTAP	NM_002451.4	c.-279A>G		upstream_gene_variant		ENST00000644715.2	NP_002442.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTAP	ENST00000644715.2	c.-279A>G		upstream_gene_variant			NM_002451.4	ENSP00000494373.1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 70729 AN: 127420 Hom.: 17318 Cov.: 23

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.458

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.525

GnomAD4 exome AF: 0.500 AC: 104775 AN: 209654 Hom.: 2047 AF XY: 0.499 AC XY: 54054 AN XY: 108350

Gnomad4 AFR exome AF: 0.510

Gnomad4 AMR exome AF: 0.507

Gnomad4 ASJ exome AF: 0.495

Gnomad4 EAS exome AF: 0.512

Gnomad4 SAS exome AF: 0.492

Gnomad4 FIN exome AF: 0.503

Gnomad4 NFE exome AF: 0.498

Gnomad4 OTH exome AF: 0.501

GnomAD4 genome AF: 0.555 AC: 70751 AN: 127424 Hom.: 17329 Cov.: 23 AF XY: 0.552 AC XY: 34306 AN XY: 62156

Gnomad4 AFR AF: 0.649

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.708

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.512

Gnomad4 OTH AF: 0.528

Alfa AF: 0.494 Hom.: 2330

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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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	-0.85
CADD	Benign	2.2
DANN	Benign	0.14

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2165408; hg19: chr9-21802469; COSMIC: COSV66477332;