rs11021499

Variant names:

• chr11-96258965-G-A
• rs11021499
• NM_032427.4:c.513+82418C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-96258965-G-A
• chr11-96258965-G-C
• chr11-96258965-G-T

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+82418C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,000 control chromosomes in the GnomAD database, including 9,268 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 0.34 (9268 hom., cov: 32)
• Consequence: MAML2 NM_032427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• Publications: 10 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAML2	NM_032427.4	c.513+82418C>T		intron_variant	Intron 1 of 4	ENST00000524717.6	NP_115803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAML2	ENST00000524717.6	c.513+82418C>T		intron_variant	Intron 1 of 4	1	NM_032427.4	ENSP00000434552.1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51365 AN: 151882 Hom.: 9268 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.338 AC: 51379 AN: 152000 Hom.: 9268 Cov.: 32 AF XY: 0.347 AC XY: 25790 AN XY: 74272

African (AFR) AF: 0.219 AC: 9066 AN: 41442

American (AMR) AF: 0.353 AC: 5401 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1200 AN: 3470

East Asian (EAS) AF: 0.528 AC: 2735 AN: 5176

South Asian (SAS) AF: 0.543 AC: 2615 AN: 4816

European-Finnish (FIN) AF: 0.437 AC: 4609 AN: 10554

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24685 AN: 67936

Other (OTH) AF: 0.325 AC: 686 AN: 2114

Alfa AF: 0.350 Hom.: 12227

Bravo AF: 0.322

Asia WGS AF: 0.462 AC: 1608 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.2
DANN	Benign	0.72
PhyloP100		0.12
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: rs11021499; hg19: chr11-95992129;