11-96178228-A-G

Variant names:

• chr11-96178228-A-G
• rs483884
• NM_032427.4:c.514-84711T>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.514-84711T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,608 control chromosomes in the GnomAD database, including 22,552 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 0.54 (22552 hom., cov: 30)
• Consequence: MAML2 NM_032427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.568
• Publications: 1 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAML2	NM_032427.4	c.514-84711T>C		intron_variant	Intron 1 of 4	ENST00000524717.6	NP_115803.1
MAML2	XM_011543023.4	c.72+51529T>C		intron_variant	Intron 1 of 4		XP_011541325.1
MAML2	XM_047427710.1	c.-172+30699T>C		intron_variant	Intron 1 of 4		XP_047283666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAML2	ENST00000524717.6	c.514-84711T>C		intron_variant	Intron 1 of 4	1	NM_032427.4	ENSP00000434552.1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82002 AN: 151492 Hom.: 22525 Cov.: 30

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.541 AC: 82082 AN: 151608 Hom.: 22552 Cov.: 30 AF XY: 0.542 AC XY: 40137 AN XY: 74066

African (AFR) AF: 0.613 AC: 25295 AN: 41294

American (AMR) AF: 0.556 AC: 8463 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1783 AN: 3460

East Asian (EAS) AF: 0.750 AC: 3869 AN: 5156

South Asian (SAS) AF: 0.480 AC: 2306 AN: 4804

European-Finnish (FIN) AF: 0.463 AC: 4853 AN: 10482

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33812 AN: 67886

Other (OTH) AF: 0.561 AC: 1180 AN: 2102

Alfa AF: 0.525 Hom.: 17964

Bravo AF: 0.556

Asia WGS AF: 0.599 AC: 2086 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	14
DANN	Benign	0.43
PhyloP100		0.57
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: rs483884; hg19: chr11-95911392;