Genetic Variant MAML2:c.*1080C>A (chr11-95977868-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0590

Publications

2 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MAML2	NM_032427.4 link	c.*1080C>A	3_prime_UTR_variant	Exon 5 of 5	ENST00000524717.6	NP_115803.1	Q8IZL2
MAML2	XM_011543023.4 link	c.*1080C>A	3_prime_UTR_variant	Exon 5 of 5		XP_011541325.1
MAML2	XM_047427710.1 link	c.*1080C>A	3_prime_UTR_variant	Exon 5 of 5		XP_047283666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAML2	ENST00000524717.6 link	c.*1080C>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_032427.4	ENSP00000434552.1		Q8IZL2

Frequencies

GnomAD3 genomes

AF:

0.237

AC:

35963

AN:

151904

Hom.:

4751

Cov.:

show subpopulations

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.:

AF XY:

0.179

AC XY:

6037

AN XY:

33736

show subpopulations

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:

AN:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

528

1056

1584

2112

2640

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.237

AC:

36026

AN:

152022

Hom.:

4766

Cov.:

AF XY:

0.243

AC XY:

18088

AN XY:

74312

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.180

AC:

12236

AN:

67956

Other (OTH)

AF:

0.229

AC:

483

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1387

2774

4160

5547

6934

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

372

744

1116

1488

1860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.176

Hom.:

1403

Bravo

AF:

0.244

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.2

(source)

DANN

Benign

0.68

PhyloP100

0.059

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over