Genetic Variant MAP7D2:p.Val624Phe (chrX-20013069-C-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001168465.2(MAP7D2):c.1870G>T(p.Val624Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,096,419 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.000045 ( 0 hom. 10 hem. )

Consequence

MAP7D2
NM_001168465.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01

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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2985362).

BS2

High Hemizygotes in GnomAdExome4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP7D2	NM_001168465.2 link	c.1870G>T	p.Val624Phe	missense_variant	Exon 14 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.1870G>T	p.Val624Phe	missense_variant	Exon 14 of 17	1	NM_001168465.2	ENSP00000368964.5	Q96T17-2
MAP7D2	ENST00000379651.7 link	c.1747G>T	p.Val583Phe	missense_variant	Exon 13 of 16	1		ENSP00000368972.3	Q96T17-1
MAP7D2	ENST00000443379.7 link	c.1612G>T	p.Val538Phe	missense_variant	Exon 12 of 15	2		ENSP00000388239.3	Q96T17-4
MAP7D2	ENST00000452324.3 link	c.1591G>T	p.Val531Phe	missense_variant	Exon 13 of 16	2		ENSP00000413301.3	Q96T17-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000550

AC:

AN:

181667

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

66155

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000447

AC:

AN:

1096419

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

361829

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000559

Gnomad4 OTH exome

AF:

0.0000435

GnomAD4 genome

Cov.:

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 16, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1870G>T (p.V624F) alteration is located in exon 14 (coding exon 14) of the MAP7D2 gene. This alteration results from a G to T substitution at nucleotide position 1870, causing the valine (V) at amino acid position 624 to be replaced by a phenylalanine (F). 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

0.083

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

T;.;.;.

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.85

D;T;D;D

M_CAP

Benign

0.037

MetaRNN

Benign

0.30

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.9

M;.;.;.

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.9

D;D;D;D

REVEL

Benign

0.10

Sift

Uncertain

0.0040

D;D;D;D

Sift4G

Uncertain

0.030

D;D;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.34

MVP

0.64

MPC

0.16

ClinPred

0.67

GERP RS

3.3

Varity_R

0.52

gMVP

0.46

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