Variant X-20015302-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001168465.2(MAP7D2):c.1670G>A(p.Arg557Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000048 in 1,208,848 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000052 ( 0 hom. 12 hem. )

Consequence

MAP7D2
NM_001168465.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.81

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06910184).

BP6

Variant X-20015302-C-T is Benign according to our data. Variant chrX-20015302-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2603621.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP7D2	NM_001168465.2 linkuse as main transcript	c.1670G>A	p.Arg557Gln	missense_variant	12/17	ENST00000379643.10	NP_001161937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP7D2	ENST00000379643.10 linkuse as main transcript	c.1670G>A	p.Arg557Gln	missense_variant	12/17	1	NM_001168465.2	ENSP00000368964	A2	Q96T17-2
MAP7D2	ENST00000379651.7 linkuse as main transcript	c.1547G>A	p.Arg516Gln	missense_variant	11/16	1		ENSP00000368972	A2	Q96T17-1
MAP7D2	ENST00000443379.7 linkuse as main transcript	c.1412G>A	p.Arg471Gln	missense_variant	10/15	2		ENSP00000388239	A2	Q96T17-4
MAP7D2	ENST00000452324.3 linkuse as main transcript	c.1391G>A	p.Arg464Gln	missense_variant	11/16	2		ENSP00000413301	P2	Q96T17-5

Frequencies

GnomAD3 genomes

AF:

0.00000893

AC:

AN:

111944

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34122

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000437

AC:

AN:

182863

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67405

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

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:

0.0000856

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000520

AC:

AN:

1096904

Hom.:

Cov.:

AF XY:

0.0000331

AC XY:

AN XY:

362312

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000370

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000594

Gnomad4 OTH exome

AF:

0.0000869

GnomAD4 genome

AF:

0.00000893

AC:

AN:

111944

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34122

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:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.85

CADD

Benign

8.6

DANN

Benign

0.91

DEOGEN2

Benign

0.070

T;.;.;.

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.85

D;T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.069

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.;.;.

MutationTaster

Benign

0.82

N;N;N;N;N

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.44

N;N;N;N

REVEL

Benign

0.033

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.58

T;T;T;T

Polyphen

0.064

B;B;.;.

Vest4

0.092

MutPred

0.61

Loss of MoRF binding (P = 0.0094);.;.;.;

MVP

0.043

MPC

0.14

ClinPred

0.032

GERP RS

0.69

Varity_R

0.031

gMVP

0.0090

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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