chr11-95977868-G-T

Variant names:

• chr11-95977868-G-T
• rs7114756
• NM_032427.4:c.*1080C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032427.4(MAML2):​c.*1080C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 225,130 control chromosomes in the GnomAD database, including 6,047 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 0.24 (4766 hom., cov: 33)
  • Exomes 𝑓: 0.18 (1281 hom.)
• Consequence: MAML2 NM_032427.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590
• 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]

MAML2 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.318 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAML2	NM_032427.4	MANE Select	c.*1080C>A		3_prime_UTR	Exon 5 of 5	NP_115803.1	Q8IZL2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAML2	ENST00000524717.6	TSL:1 MANE Select	c.*1080C>A		3_prime_UTR	Exon 5 of 5	ENSP00000434552.1	Q8IZL2

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35963 AN: 151904 Hom.: 4751 Cov.: 33

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.229

GnomAD4 exome AF: 0.181 AC: 13250 AN: 73108 Hom.: 1281 Cov.: 0 AF XY: 0.179 AC XY: 6037 AN XY: 33736

African (AFR) AF: 0.310 AC: 1084 AN: 3492

American (AMR) AF: 0.324 AC: 720 AN: 2220

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 682 AN: 4616

East Asian (EAS) AF: 0.118 AC: 1235 AN: 10462

South Asian (SAS) AF: 0.200 AC: 125 AN: 626

European-Finnish (FIN) AF: 0.190 AC: 11 AN: 58

Middle Eastern (MID) AF: 0.229 AC: 101 AN: 442

European-Non Finnish (NFE) AF: 0.180 AC: 8102 AN: 45104

Other (OTH) AF: 0.195 AC: 1190 AN: 6088

GnomAD4 genome AF: 0.237 AC: 36026 AN: 152022 Hom.: 4766 Cov.: 33 AF XY: 0.243 AC XY: 18088 AN XY: 74312

African (AFR) AF: 0.308 AC: 12779 AN: 41452

American (AMR) AF: 0.325 AC: 4969 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 463 AN: 3470

East Asian (EAS) AF: 0.132 AC: 682 AN: 5172

South Asian (SAS) AF: 0.223 AC: 1077 AN: 4826

European-Finnish (FIN) AF: 0.282 AC: 2977 AN: 10554

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12236 AN: 67956

Other (OTH) AF: 0.229 AC: 483 AN: 2112

Alfa AF: 0.176 Hom.: 1403

Bravo AF: 0.244

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.68
PhyloP100		0.059
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: rs7114756; hg19: chr11-95711032;