rs2509000

Variant names:

• chr11-96290857-G-A
• rs2509000
• NM_032427.4:c.513+50526C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-96290857-G-A
• chr11-96290857-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032427.4(MAML2):​c.513+50526C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 151,886 control chromosomes in the GnomAD database, including 40,363 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.73 (40363 hom., cov: 30)
• Consequence: MAML2 NM_032427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191
• Publications: 2 publications found

Genes affected

MAML2 (HGNC:16259): (mastermind like transcriptional coactivator 2) The protein encoded by this gene is a member of the Mastermind-like family of proteins. All family members are proline and glutamine-rich, and contain a conserved basic domain that binds the ankyrin repeat domain of the intracellular domain of the Notch receptors (ICN1-4) in their N-terminus, and a transcriptional activation domain in their C-terminus. This protein binds to an extended groove that is formed by the interaction of CBF1, Suppressor of Hairless, LAG-1 (CSL) with ICN, and positively regulates Notch signaling. High levels of expression of this gene have been observed in several B cell-derived lymphomas. Translocations resulting in fusion proteins with both CRTC1 and CRTC3 have been implicated in the development of mucoepidermoid carcinomas, while a translocation event with CXCR4 has been linked with chronic lymphocytic leukemia (CLL). Copy number variation in the polyglutamine tract has been observed. [provided by RefSeq, Jan 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032427.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAML2	NM_032427.4	MANE Select	c.513+50526C>T		intron	N/A	NP_115803.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAML2	ENST00000524717.6	TSL:1 MANE Select	c.513+50526C>T		intron	N/A	ENSP00000434552.1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110370 AN: 151768 Hom.: 40331 Cov.: 30

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.766

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.727 AC: 110448 AN: 151886 Hom.: 40363 Cov.: 30 AF XY: 0.730 AC XY: 54148 AN XY: 74202

African (AFR) AF: 0.651 AC: 26929 AN: 41376

American (AMR) AF: 0.714 AC: 10888 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 2632 AN: 3472

East Asian (EAS) AF: 0.849 AC: 4381 AN: 5162

South Asian (SAS) AF: 0.828 AC: 3984 AN: 4814

European-Finnish (FIN) AF: 0.744 AC: 7846 AN: 10548

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.756 AC: 51371 AN: 67954

Other (OTH) AF: 0.721 AC: 1521 AN: 2110

Alfa AF: 0.747 Hom.: 179061

Bravo AF: 0.716

Asia WGS AF: 0.803 AC: 2791 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.24
DANN	Benign	0.15
PhyloP100		-0.19
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: rs2509000; hg19: chr11-96024021;