Genetic Variant MAP7D2:p.Arg564Ser (chrX-20015282-G-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.1690C>A(p.Arg564Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000091 in 1,209,090 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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. R564H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000082 ( 0 hom. 2 hem. )

Consequence

MAP7D2
NM_001168465.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.66

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:

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 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP7D2	NM_001168465.2 link	c.1690C>A	p.Arg564Ser	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.1690C>A	p.Arg564Ser	missense_variant	Exon 12 of 17	1	NM_001168465.2	ENSP00000368964.5	Q96T17-2
MAP7D2	ENST00000379651.7 link	c.1567C>A	p.Arg523Ser	missense_variant	Exon 11 of 16	1		ENSP00000368972.3	Q96T17-1
MAP7D2	ENST00000443379.7 link	c.1432C>A	p.Arg478Ser	missense_variant	Exon 10 of 15	2		ENSP00000388239.3	Q96T17-4
MAP7D2	ENST00000452324.3 link	c.1411C>A	p.Arg471Ser	missense_variant	Exon 11 of 16	2		ENSP00000413301.3	Q96T17-5

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111634

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33840

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

183021

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67533

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000134

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:

0.00000820

AC:

AN:

1097456

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

362856

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000516

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000951

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111634

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33840

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000376

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 19, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1690C>A (p.R564S) alteration is located in exon 12 (coding exon 12) of the MAP7D2 gene. This alteration results from a C to A substitution at nucleotide position 1690, causing the arginine (R) at amino acid position 564 to be replaced by a serine (S). 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

0.82

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

T;.;.;.

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.97

D;D;D;D

M_CAP

Benign

0.067

MetaRNN

Uncertain

0.72

D;D;D;D

MetaSVM

Benign

-0.56

MutationAssessor

Pathogenic

3.5

H;.;.;.

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-5.7

D;D;D;D

REVEL

Uncertain

0.46

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.85

MutPred

0.51

Loss of MoRF binding (P = 0.0104);.;.;.;

MVP

0.81

MPC

0.14

ClinPred

0.96

GERP RS

4.7

Varity_R

0.92

gMVP

0.17

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