rs485642

Positions:

• chr11-96245055-A-G

Variant summary

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

The ENST00000524717.6(MAML2):​c.513+96328T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,006 control chromosomes in the GnomAD database, including 6,901 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 0.30 (6901 hom., cov: 32)
• Consequence: MAML2 ENST00000524717.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAML2	NM_032427.4	c.513+96328T>C		intron_variant		ENST00000524717.6	NP_115803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAML2	ENST00000524717.6	c.513+96328T>C		intron_variant		1	NM_032427.4	ENSP00000434552	P1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45215 AN: 151888 Hom.: 6892 Cov.: 32

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.298 AC: 45246 AN: 152006 Hom.: 6901 Cov.: 32 AF XY: 0.298 AC XY: 22158 AN XY: 74300

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.282

Alfa AF: 0.299 Hom.: 3411

Bravo AF: 0.304

Asia WGS AF: 0.351 AC: 1219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.31
DANN	Benign	0.83

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: rs485642; hg19: chr11-95978219;