rs508643

Variant names:

• chr11-96228580-A-G
• rs508643
• NM_032427.4:c.513+112803T>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+112803T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 152,138 control chromosomes in the GnomAD database, including 37,017 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 0.69 (37017 hom., cov: 32)
• Consequence: MAML2 NM_032427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.674
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.838 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+112803T>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+112803T>C		intron	N/A	ENSP00000434552.1

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104715 AN: 152020 Hom.: 36979 Cov.: 32

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.689 AC: 104812 AN: 152138 Hom.: 37017 Cov.: 32 AF XY: 0.685 AC XY: 50969 AN XY: 74366

African (AFR) AF: 0.845 AC: 35104 AN: 41530

American (AMR) AF: 0.708 AC: 10822 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2175 AN: 3470

East Asian (EAS) AF: 0.613 AC: 3167 AN: 5166

South Asian (SAS) AF: 0.501 AC: 2416 AN: 4820

European-Finnish (FIN) AF: 0.599 AC: 6332 AN: 10570

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42653 AN: 67972

Other (OTH) AF: 0.700 AC: 1482 AN: 2116

Alfa AF: 0.667 Hom.: 4476

Bravo AF: 0.707

Asia WGS AF: 0.536 AC: 1863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.43
PhyloP100		-0.67
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: rs508643; hg19: chr11-95961744;