Genetic Variant NM_001168465.2:c.1706A>G (chrX-20015266-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001168465.2(MAP7D2):c.1706A>G(p.Gln569Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000024 in 1,209,657 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 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 0.000063 ( 0 hom., 3 hem., cov: 22)

Exomes 𝑓: 0.000020 ( 0 hom. 6 hem. )

Consequence

MAP7D2
NM_001168465.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017866284).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP7D2	NM_001168465.2 link	c.1706A>G	p.Gln569Arg	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.1706A>G	p.Gln569Arg	missense_variant	Exon 12 of 17	1	NM_001168465.2	ENSP00000368964.5	Q96T17-2
MAP7D2	ENST00000379651.7 link	c.1583A>G	p.Gln528Arg	missense_variant	Exon 11 of 16	1		ENSP00000368972.3	Q96T17-1
MAP7D2	ENST00000443379.7 link	c.1448A>G	p.Gln483Arg	missense_variant	Exon 10 of 15	2		ENSP00000388239.3	Q96T17-4
MAP7D2	ENST00000452324.3 link	c.1427A>G	p.Gln476Arg	missense_variant	Exon 11 of 16	2		ENSP00000413301.3	Q96T17-5

Frequencies

GnomAD3 genomes

AF:

0.0000625

AC:

AN:

111930

Hom.:

Cov.:

AF XY:

0.0000880

AC XY:

AN XY:

34090

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:

0.00196

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:

0.000147

AC:

AN:

183135

Hom.:

AF XY:

0.000192

AC XY:

AN XY:

67607

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00195

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000200

AC:

AN:

1097727

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

363107

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000728

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000625

AC:

AN:

111930

Hom.:

Cov.:

AF XY:

0.0000880

AC XY:

AN XY:

34090

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00196

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000718

ExAC

AF:

0.000206

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1706A>G (p.Q569R) alteration is located in exon 12 (coding exon 12) of the MAP7D2 gene. This alteration results from a A to G substitution at nucleotide position 1706, causing the glutamine (Q) at amino acid position 569 to be replaced by an arginine (R). 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

0.12

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.051

T;.;.;.

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.70

T;T;T;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.018

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.;.;.

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.2

N;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.42

T;T;T;T

Sift4G

Benign

0.60

T;T;T;T

Polyphen

0.99

D;D;.;.

Vest4

0.35

MutPred

0.35

Gain of MoRF binding (P = 0.0298);.;.;.;

MVP

0.35

MPC

0.13

ClinPred

0.11

GERP RS

5.6

Varity_R

0.48

gMVP

0.031

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