11-96133536-G-C

Position:

• chr11-96133536-G-C

Variant summary

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

The NM_032427.4(MAML2):​c.514-40019C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 151,622 control chromosomes in the GnomAD database, including 1,277 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 0.11 (1277 hom., cov: 32)
• Consequence: MAML2 NM_032427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAML2	NM_032427.4	c.514-40019C>G		intron_variant		ENST00000524717.6
MAML2	XM_011543023.4	c.73-40019C>G		intron_variant
MAML2	XM_047427710.1	c.-171-40019C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAML2	ENST00000524717.6	c.514-40019C>G		intron_variant		1	NM_032427.4	P1
	ENST00000648443.1	n.550-1715G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16244 AN: 151504 Hom.: 1275 Cov.: 32

Gnomad AFR AF: 0.0209

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.0910

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.107 AC: 16257 AN: 151622 Hom.: 1277 Cov.: 32 AF XY: 0.114 AC XY: 8461 AN XY: 74076

Gnomad4 AFR AF: 0.0209

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.0910

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.105

Alfa AF: 0.113 Hom.: 660

Bravo AF: 0.109

Asia WGS AF: 0.155 AC: 540 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10765792; hg19: chr11-95866700;