X-20012356-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001168465.2(MAP7D2):​c.2065G>A​(p.Asp689Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000461 in 1,083,892 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 0.0000046 ( 0 hom. 3 hem. )

Consequence

MAP7D2
NM_001168465.2 missense

Scores

3
8
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.84
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 -4 ACMG points.

BS2
High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAP7D2NM_001168465.2 linkc.2065G>A p.Asp689Asn missense_variant Exon 15 of 17 ENST00000379643.10 NP_001161937.1 Q96T17-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAP7D2ENST00000379643.10 linkc.2065G>A p.Asp689Asn missense_variant Exon 15 of 17 1 NM_001168465.2 ENSP00000368964.5 Q96T17-2
MAP7D2ENST00000379651.7 linkc.1942G>A p.Asp648Asn missense_variant Exon 14 of 16 1 ENSP00000368972.3 Q96T17-1
MAP7D2ENST00000443379.7 linkc.1807G>A p.Asp603Asn missense_variant Exon 13 of 15 2 ENSP00000388239.3 Q96T17-4
MAP7D2ENST00000452324.3 linkc.1786G>A p.Asp596Asn missense_variant Exon 14 of 16 2 ENSP00000413301.3 Q96T17-5

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
AF:
0.00000461
AC:
5
AN:
1083892
Hom.:
0
Cov.:
28
AF XY:
0.00000855
AC XY:
3
AN XY:
350954
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00000600
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
23

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 28, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2065G>A (p.D689N) alteration is located in exon 15 (coding exon 15) of the MAP7D2 gene. This alteration results from a G to A substitution at nucleotide position 2065, causing the aspartic acid (D) at amino acid position 689 to be replaced by an asparagine (N). 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
Pathogenic
0.77
BayesDel_addAF
Benign
-0.073
T
BayesDel_noAF
Benign
-0.34
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.32
T;.;.;.
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.97
D;D;D;D
M_CAP
Uncertain
0.20
D
MetaRNN
Benign
0.39
T;T;T;T
MetaSVM
Uncertain
0.55
D
MutationAssessor
Uncertain
2.1
M;.;.;.
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-2.2
N;N;D;N
REVEL
Uncertain
0.44
Sift
Uncertain
0.0080
D;D;D;D
Sift4G
Uncertain
0.034
D;D;D;D
Polyphen
1.0
D;D;.;.
Vest4
0.41
MutPred
0.30
Loss of phosphorylation at S650 (P = 0.1387);.;.;.;
MVP
0.86
MPC
0.12
ClinPred
0.91
D
GERP RS
5.5
Varity_R
0.46
gMVP
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.33
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.33
Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-20030474; API