11-96286316-T-G

Variant names:

• chr11-96286316-T-G
• rs522475
• NM_032427.4:c.513+55067A>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+55067A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 151,980 control chromosomes in the GnomAD database, including 37,912 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 0.71 (37912 hom., cov: 31)
• Consequence: MAML2 NM_032427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 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+55067A>C		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+55067A>C		intron	N/A	ENSP00000434552.1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107100 AN: 151862 Hom.: 37881 Cov.: 31

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.705 AC: 107179 AN: 151980 Hom.: 37912 Cov.: 31 AF XY: 0.706 AC XY: 52443 AN XY: 74282

African (AFR) AF: 0.648 AC: 26849 AN: 41422

American (AMR) AF: 0.694 AC: 10605 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2531 AN: 3472

East Asian (EAS) AF: 0.829 AC: 4289 AN: 5172

South Asian (SAS) AF: 0.687 AC: 3302 AN: 4804

European-Finnish (FIN) AF: 0.717 AC: 7568 AN: 10558

Middle Eastern (MID) AF: 0.671 AC: 196 AN: 292

European-Non Finnish (NFE) AF: 0.731 AC: 49658 AN: 67960

Other (OTH) AF: 0.702 AC: 1483 AN: 2112

Alfa AF: 0.696 Hom.: 6022

Bravo AF: 0.699

Asia WGS AF: 0.725 AC: 2520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.28
PhyloP100		-0.20
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: rs522475; hg19: chr11-96019480;