rs7120279

Positions:

• chr11-95987111-T-C
• chr11-95987111-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_032427.4(MAML2):​c.2344-1469A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,940 control chromosomes in the GnomAD database, including 10,459 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 0.34 (10459 hom., cov: 32)
• Consequence: MAML2 NM_032427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAML2	NM_032427.4	c.2344-1469A>G		intron_variant		ENST00000524717.6
MAML2	XM_011543023.4	c.1903-1469A>G		intron_variant
MAML2	XM_047427710.1	c.1660-1469A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAML2	ENST00000524717.6	c.2344-1469A>G		intron_variant		1	NM_032427.4	P1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50906 AN: 151822 Hom.: 10450 Cov.: 32

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.335 AC: 50954 AN: 151940 Hom.: 10459 Cov.: 32 AF XY: 0.340 AC XY: 25220 AN XY: 74240

Gnomad4 AFR AF: 0.574

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.301

Alfa AF: 0.256 Hom.: 3116

Bravo AF: 0.345

Asia WGS AF: 0.390 AC: 1357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	13
DANN	Benign	0.91

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: rs7120279; hg19: chr11-95720275;