X-20011024-T-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001168465.2(MAP7D2):ā€‹c.2101A>Cā€‹(p.Ile701Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000232 in 1,208,586 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00016 ( 0 hom., 3 hem., cov: 23)
Exomes š‘“: 0.0000091 ( 0 hom. 3 hem. )

Consequence

MAP7D2
NM_001168465.2 missense

Scores

2
8
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.91
Variant links:
Genes affected
MAP7D2 (HGNC:25899): (MAP7 domain containing 2) Predicted to be involved in microtubule cytoskeleton organization. Predicted to be active in microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.24173322).
BS2
High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MAP7D2NM_001168465.2 linkuse as main transcriptc.2101A>C p.Ile701Leu missense_variant 16/17 ENST00000379643.10 NP_001161937.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MAP7D2ENST00000379643.10 linkuse as main transcriptc.2101A>C p.Ile701Leu missense_variant 16/171 NM_001168465.2 ENSP00000368964 A2Q96T17-2
MAP7D2ENST00000379651.7 linkuse as main transcriptc.1978A>C p.Ile660Leu missense_variant 15/161 ENSP00000368972 A2Q96T17-1
MAP7D2ENST00000443379.7 linkuse as main transcriptc.1843A>C p.Ile615Leu missense_variant 14/152 ENSP00000388239 A2Q96T17-4
MAP7D2ENST00000452324.3 linkuse as main transcriptc.1822A>C p.Ile608Leu missense_variant 15/162 ENSP00000413301 P2Q96T17-5

Frequencies

GnomAD3 genomes
AF:
0.000161
AC:
18
AN:
111700
Hom.:
0
Cov.:
23
AF XY:
0.0000885
AC XY:
3
AN XY:
33890
show subpopulations
Gnomad AFR
AF:
0.000586
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000383
AC:
7
AN:
182991
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
67537
show subpopulations
Gnomad AFR exome
AF:
0.000533
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000912
AC:
10
AN:
1096886
Hom.:
0
Cov.:
29
AF XY:
0.00000828
AC XY:
3
AN XY:
362266
show subpopulations
Gnomad4 AFR exome
AF:
0.000228
Gnomad4 AMR exome
AF:
0.0000568
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000434
GnomAD4 genome
AF:
0.000161
AC:
18
AN:
111700
Hom.:
0
Cov.:
23
AF XY:
0.0000885
AC XY:
3
AN XY:
33890
show subpopulations
Gnomad4 AFR
AF:
0.000586
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000174
Hom.:
1
Bravo
AF:
0.000117
ESP6500AA
AF:
0.00104
AC:
4
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000659
AC:
8

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 02, 2022The c.2101A>C (p.I701L) alteration is located in exon 16 (coding exon 16) of the MAP7D2 gene. This alteration results from a A to C substitution at nucleotide position 2101, causing the isoleucine (I) at amino acid position 701 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.51
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Uncertain
0.0
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.24
T;.;.;.
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.93
D;D;D;D
M_CAP
Uncertain
0.18
D
MetaRNN
Benign
0.24
T;T;T;T
MetaSVM
Uncertain
0.59
D
MutationAssessor
Uncertain
2.1
M;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-0.73
N;N;N;N
REVEL
Uncertain
0.53
Sift
Benign
0.079
T;T;T;T
Sift4G
Benign
0.40
T;T;T;T
Polyphen
1.0
D;D;.;.
Vest4
0.57
MVP
0.86
MPC
0.12
ClinPred
0.19
T
GERP RS
5.2
Varity_R
0.48
gMVP
0.58

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: rs143010630; hg19: chrX-20029142; API