Variant X-20012482-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001168465.2(MAP7D2):c.1939C>G(p.Pro647Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000183 in 1,204,400 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.000015 ( 0 hom. 3 hem. )

Consequence

MAP7D2
NM_001168465.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09768012).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP7D2	NM_001168465.2 linkuse as main transcript	c.1939C>G	p.Pro647Ala	missense_variant	15/17	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.1939C>G	p.Pro647Ala	missense_variant	15/17	1	NM_001168465.2	ENSP00000368964	A2	Q96T17-2
MAP7D2	ENST00000379651.7 linkuse as main transcript	c.1816C>G	p.Pro606Ala	missense_variant	14/16	1		ENSP00000368972	A2	Q96T17-1
MAP7D2	ENST00000443379.7 linkuse as main transcript	c.1681C>G	p.Pro561Ala	missense_variant	13/15	2		ENSP00000388239	A2	Q96T17-4
MAP7D2	ENST00000452324.3 linkuse as main transcript	c.1660C>G	p.Pro554Ala	missense_variant	14/16	2		ENSP00000413301	P2	Q96T17-5

Frequencies

GnomAD3 genomes

AF:

0.0000538

AC:

AN:

111518

Hom.:

Cov.:

AF XY:

0.0000889

AC XY:

AN XY:

33742

show subpopulations

Gnomad AFR

AF:

0.000163

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:

0.0000339

AC:

AN:

177232

Hom.:

AF XY:

0.0000323

AC XY:

AN XY:

62000

show subpopulations

Gnomad AFR exome

AF:

0.000154

Gnomad AMR exome

AF:

0.0000384

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000745

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000250

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000146

AC:

AN:

1092882

Hom.:

Cov.:

AF XY:

0.00000837

AC XY:

AN XY:

358526

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.0000289

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000999

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000107

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000538

AC:

AN:

111518

Hom.:

Cov.:

AF XY:

0.0000889

AC XY:

AN XY:

33742

show subpopulations

Gnomad4 AFR

AF:

0.000163

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

Alfa

AF:

0.000162

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2024

The c.1939C>G (p.P647A) alteration is located in exon 15 (coding exon 15) of the MAP7D2 gene. This alteration results from a C to G substitution at nucleotide position 1939, causing the proline (P) at amino acid position 647 to be replaced by an alanine (A). 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

0.062

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;.;.;.

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.70

T;T;T;T

M_CAP

Benign

0.0071

MetaRNN

Benign

0.098

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

M;.;.;.

MutationTaster

Benign

0.98

N;N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-2.3

N;D;N;N

REVEL

Benign

0.031

Sift

Benign

0.29

T;T;T;T

Sift4G

Benign

0.39

T;T;T;T

Polyphen

0.83

P;D;.;.

Vest4

0.17

MVP

0.29

MPC

0.12

ClinPred

0.097

GERP RS

4.3

Varity_R

0.077

gMVP

0.21

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