X-20025026-G-C

Position:

• chrX-20025026-G-C

Variant summary

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

The NM_001168465.2(MAP7D2):​c.1337C>G​(p.Ala446Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: MAP7D2 NM_001168465.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.99

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]

ACMG classification

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/exons	MANE	Protein	UniProt
MAP7D2	NM_001168465.2	c.1337C>G	p.Ala446Gly	missense_variant	10/17	ENST00000379643.10	NP_001161937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP7D2	ENST00000379643.10	c.1337C>G	p.Ala446Gly	missense_variant	10/17	1	NM_001168465.2	ENSP00000368964	A2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 23, 2023

The c.1337C>G (p.A446G) alteration is located in exon 10 (coding exon 10) of the MAP7D2 gene. This alteration results from a C to G substitution at nucleotide position 1337, causing the alanine (A) at amino acid position 446 to be replaced by a glycine (G). 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	Uncertain	0.37
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T;.;.;.
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Pathogenic	0.55	D
MetaRNN	Uncertain	0.61	D;D;D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Pathogenic	3.5	H;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.6	D;D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0050	D;D;D;D
Sift4G	Uncertain	0.0080	D;D;D;D
Polyphen		0.95	P;P;.;.
Vest4		0.48
MutPred		0.64		Loss of ubiquitination at K407 (P = 0.1055);.;.;.;
MVP		0.55
MPC		0.57
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.59
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-20043144; COSMIC: COSV65529675;