11-96133536-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032427.4(MAML2):​c.514-40019C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 151,622 control chromosomes in the GnomAD database, including 1,277 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 0.11 ( 1277 hom., cov: 32)

Consequence

MAML2
NM_032427.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0850
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MAML2NM_032427.4 linkuse as main transcriptc.514-40019C>G intron_variant ENST00000524717.6
MAML2XM_011543023.4 linkuse as main transcriptc.73-40019C>G intron_variant
MAML2XM_047427710.1 linkuse as main transcriptc.-171-40019C>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MAML2ENST00000524717.6 linkuse as main transcriptc.514-40019C>G intron_variant 1 NM_032427.4 P1
ENST00000648443.1 linkuse as main transcriptn.550-1715G>C intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.107
AC:
16244
AN:
151504
Hom.:
1275
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0209
Gnomad AMI
AF:
0.186
Gnomad AMR
AF:
0.218
Gnomad ASJ
AF:
0.0910
Gnomad EAS
AF:
0.276
Gnomad SAS
AF:
0.102
Gnomad FIN
AF:
0.195
Gnomad MID
AF:
0.0538
Gnomad NFE
AF:
0.109
Gnomad OTH
AF:
0.105
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.107
AC:
16257
AN:
151622
Hom.:
1277
Cov.:
32
AF XY:
0.114
AC XY:
8461
AN XY:
74076
show subpopulations
Gnomad4 AFR
AF:
0.0209
Gnomad4 AMR
AF:
0.219
Gnomad4 ASJ
AF:
0.0910
Gnomad4 EAS
AF:
0.277
Gnomad4 SAS
AF:
0.102
Gnomad4 FIN
AF:
0.195
Gnomad4 NFE
AF:
0.109
Gnomad4 OTH
AF:
0.105
Alfa
AF:
0.113
Hom.:
660
Bravo
AF:
0.109
Asia WGS
AF:
0.155
AC:
540
AN:
3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
4.7
DANN
Benign
0.44

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10765792; hg19: chr11-95866700; API