Genetic Variant MAP7D2:p.Arg564His (chrX-20015281-C-T) – ACMG Classification: Likely_benign (-4 pts)

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

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]

MAP7D2 links:

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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
MAP7D2	NM_001168465.2 link	c.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	UniProt
MAP7D2	ENST00000379643.10 link	c.1691G>A	p.Arg564His	missense_variant	Exon 12 of 17	1	NM_001168465.2	ENSP00000368964.5	Q96T17-2
MAP7D2	ENST00000379651.7 link	c.1568G>A	p.Arg523His	missense_variant	Exon 11 of 16	1		ENSP00000368972.3	Q96T17-1
MAP7D2	ENST00000443379.7 link	c.1433G>A	p.Arg478His	missense_variant	Exon 10 of 15	2		ENSP00000388239.3	Q96T17-4
MAP7D2	ENST00000452324.3 link	c.1412G>A	p.Arg471His	missense_variant	Exon 11 of 16	2		ENSP00000413301.3	Q96T17-5

Frequencies

GnomAD3 genomes

AF:

0.0000358

AC:

AN:

111844

Hom.:

Cov.:

AF XY:

0.0000588

AC XY:

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:

AN:

183057

Hom.:

AF XY:

0.0000296

AC XY:

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:

AN:

1097624

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

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:

AN:

111844

Hom.:

Cov.:

AF XY:

0.0000588

AC XY:

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:

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

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

T;.;.;.

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.91

D;D;D;D

M_CAP

Benign

0.060

MetaRNN

Uncertain

0.58

D;D;D;D

MetaSVM

Benign

-0.38

MutationAssessor

Pathogenic

3.5

H;.;.;.

PrimateAI

Benign

0.40

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over