X-20015281-C-T

Variant summary

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

The NM_001168465.2(MAP7D2):​c.1691G>A​(p.Arg564His) variant causes a missense change. The variant allele was found at a frequency of 0.0000215 in 1,209,468 control chromosomes in the GnomAD database, including 1 homozygotes. There are 6 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R564S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 2 hem., cov: 24)
Exomes 𝑓: 0.000020 ( 1 hom. 4 hem. )

Consequence

MAP7D2
NM_001168465.2 missense

Scores

2
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.21
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 GnomAd4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAP7D2NM_001168465.2 linkc.1691G>A p.Arg564His missense_variant Exon 12 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.1691G>A p.Arg564His missense_variant Exon 12 of 17 1 NM_001168465.2 ENSP00000368964.5 Q96T17-2
MAP7D2ENST00000379651.7 linkc.1568G>A p.Arg523His missense_variant Exon 11 of 16 1 ENSP00000368972.3 Q96T17-1
MAP7D2ENST00000443379.7 linkc.1433G>A p.Arg478His missense_variant Exon 10 of 15 2 ENSP00000388239.3 Q96T17-4
MAP7D2ENST00000452324.3 linkc.1412G>A p.Arg471His missense_variant Exon 11 of 16 2 ENSP00000413301.3 Q96T17-5

Frequencies

GnomAD3 genomes
AF:
0.0000358
AC:
4
AN:
111844
Hom.:
0
Cov.:
24
AF XY:
0.0000588
AC XY:
2
AN XY:
34002
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000379
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:
0.0000656
AC:
12
AN:
183057
Hom.:
1
AF XY:
0.0000296
AC XY:
2
AN XY:
67545
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000401
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:
0.0000122
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000200
AC:
22
AN:
1097624
Hom.:
1
Cov.:
29
AF XY:
0.0000110
AC XY:
4
AN XY:
363012
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000426
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000331
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000475
Gnomad4 OTH exome
AF:
0.0000434
GnomAD4 genome
AF:
0.0000358
AC:
4
AN:
111844
Hom.:
0
Cov.:
24
AF XY:
0.0000588
AC XY:
2
AN XY:
34002
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000379
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
Bravo
AF:
0.0000491
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1691G>A (p.R564H) alteration is located in exon 12 (coding exon 12) of the MAP7D2 gene. This alteration results from a G to A substitution at nucleotide position 1691, causing the arginine (R) at amino acid position 564 to be replaced by a histidine (H). 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
Benign
0.16
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.11
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.35
T;.;.;.
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.91
D;D;D;D
M_CAP
Benign
0.060
D
MetaRNN
Uncertain
0.58
D;D;D;D
MetaSVM
Benign
-0.38
T
MutationAssessor
Pathogenic
3.5
H;.;.;.
PrimateAI
Benign
0.40
T
PROVEAN
Pathogenic
-4.8
D;D;D;D
REVEL
Uncertain
0.58
Sift
Uncertain
0.0020
D;D;D;D
Sift4G
Uncertain
0.0020
D;D;D;D
Polyphen
1.0
D;D;.;.
Vest4
0.65
MutPred
0.59
Loss of MoRF binding (P = 0.0079);.;.;.;
MVP
0.65
MPC
0.15
ClinPred
0.80
D
GERP RS
4.7
Varity_R
0.72
gMVP
0.071

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

LitVar

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

Other links and lift over

dbSNP: rs774928077; hg19: chrX-20033399; COSMIC: COSV65530773; COSMIC: COSV65530773; API