rs1940153

Variant names:

• chr11-96056795-G-A
• rs1940153
• NM_032427.4:c.2139+35097C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_032427.4(MAML2):​c.2139+35097C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,920 control chromosomes in the GnomAD database, including 17,640 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 0.47 (17640 hom., cov: 32)
• Consequence: MAML2 NM_032427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.64
• Publications: 3 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]

ENSG00000304880 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAML2	NM_032427.4	c.2139+35097C>T		intron_variant	Intron 2 of 4	ENST00000524717.6	NP_115803.1
MAML2	XM_011543023.4	c.1698+35097C>T		intron_variant	Intron 2 of 4		XP_011541325.1
MAML2	XM_047427710.1	c.1455+35097C>T		intron_variant	Intron 2 of 4		XP_047283666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAML2	ENST00000524717.6	c.2139+35097C>T		intron_variant	Intron 2 of 4	1	NM_032427.4	ENSP00000434552.1
ENSG00000304880	ENST00000806867.1	n.154+876G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70808 AN: 151802 Hom.: 17635 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.466 AC: 70827 AN: 151920 Hom.: 17640 Cov.: 32 AF XY: 0.457 AC XY: 33914 AN XY: 74256

African (AFR) AF: 0.335 AC: 13860 AN: 41412

American (AMR) AF: 0.455 AC: 6945 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1774 AN: 3470

East Asian (EAS) AF: 0.118 AC: 611 AN: 5178

South Asian (SAS) AF: 0.350 AC: 1687 AN: 4824

European-Finnish (FIN) AF: 0.450 AC: 4736 AN: 10522

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.581 AC: 39483 AN: 67938

Other (OTH) AF: 0.513 AC: 1081 AN: 2108

Alfa AF: 0.537 Hom.: 28438

Bravo AF: 0.457

Asia WGS AF: 0.269 AC: 936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Benign	0.76
PhyloP100		2.6
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: rs1940153; hg19: chr11-95789959;