11-96266936-G-A

Position:

• chr11-96266936-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032427.4(MAML2):​c.513+74447C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,024 control chromosomes in the GnomAD database, including 10,514 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 0.37 (10514 hom., cov: 32)
• Consequence: MAML2 NM_032427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0200

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAML2	NM_032427.4	c.513+74447C>T		intron_variant		ENST00000524717.6	NP_115803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAML2	ENST00000524717.6	c.513+74447C>T		intron_variant		1	NM_032427.4	ENSP00000434552.1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55850 AN: 151906 Hom.: 10499 Cov.: 32

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.368 AC: 55894 AN: 152024 Hom.: 10514 Cov.: 32 AF XY: 0.370 AC XY: 27505 AN XY: 74294

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.357

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.336

Alfa AF: 0.339 Hom.: 17982

Bravo AF: 0.378

Asia WGS AF: 0.429 AC: 1490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs7115578; hg19: chr11-96000100;