Genetic Variant MAP7D2:p.Ser743Cys (chrX-20010897-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001168465.2(MAP7D2):c.2228C>G(p.Ser743Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000413 in 1,209,327 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000027 ( 0 hom. 0 hem. )

Consequence

MAP7D2
NM_001168465.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.55

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP7D2	NM_001168465.2 link	c.2228C>G	p.Ser743Cys	missense_variant	Exon 16 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.2228C>G	p.Ser743Cys	missense_variant	Exon 16 of 17	1	NM_001168465.2	ENSP00000368964.5	Q96T17-2
MAP7D2	ENST00000379651.7 link	c.2105C>G	p.Ser702Cys	missense_variant	Exon 15 of 16	1		ENSP00000368972.3	Q96T17-1
MAP7D2	ENST00000443379.7 link	c.1970C>G	p.Ser657Cys	missense_variant	Exon 14 of 15	2		ENSP00000388239.3	Q96T17-4
MAP7D2	ENST00000452324.3 link	c.1949C>G	p.Ser650Cys	missense_variant	Exon 15 of 16	2		ENSP00000413301.3	Q96T17-5

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111579

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33777

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

GnomAD4 exome

AF:

0.00000273

AC:

AN:

1097748

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363170

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:

0.00000356

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111579

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33777

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:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2228C>G (p.S743C) alteration is located in exon 16 (coding exon 16) of the MAP7D2 gene. This alteration results from a C to G substitution at nucleotide position 2228, causing the serine (S) at amino acid position 743 to be replaced by a cysteine (C). 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

0.14

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.19

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

T;.;.;.

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

D;D;D;D

M_CAP

Uncertain

0.22

MetaRNN

Uncertain

0.49

T;T;T;T

MetaSVM

Uncertain

0.75

MutationAssessor

Benign

0.97

L;.;.;.

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.7

D;D;D;D

REVEL

Uncertain

0.55

Sift

Uncertain

0.0080

D;D;D;D

Sift4G

Uncertain

0.018

D;D;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.51

MutPred

0.17

Loss of phosphorylation at S702 (P = 0.026);.;.;.;

MVP

0.96

MPC

0.12

ClinPred

0.96

GERP RS

5.4

Varity_R

0.44

gMVP

0.54

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