X-20010990-G-A

Position:

• chrX-20010990-G-A

Variant summary

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

The NM_001168465.2(MAP7D2):​c.2135C>T​(p.Pro712Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: MAP7D2 NM_001168465.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.75

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.2135C>T	p.Pro712Leu	missense_variant	16/17	ENST00000379643.10	NP_001161937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP7D2	ENST00000379643.10	c.2135C>T	p.Pro712Leu	missense_variant	16/17	1	NM_001168465.2	ENSP00000368964	A2
MAP7D2	ENST00000379651.7	c.2012C>T	p.Pro671Leu	missense_variant	15/16	1		ENSP00000368972	A2
MAP7D2	ENST00000443379.7	c.1877C>T	p.Pro626Leu	missense_variant	14/15	2		ENSP00000388239	A2
MAP7D2	ENST00000452324.3	c.1856C>T	p.Pro619Leu	missense_variant	15/16	2		ENSP00000413301	P2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 22

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

Dec 19, 2022

The c.2135C>T (p.P712L) alteration is located in exon 16 (coding exon 16) of the MAP7D2 gene. This alteration results from a C to T substitution at nucleotide position 2135, causing the proline (P) at amino acid position 712 to be replaced by a leucine (L). 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	0.23
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T;.;.;.
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Pathogenic	0.30	D
MetaRNN	Uncertain	0.69	D;D;D;D
MetaSVM	Uncertain	0.67	D
MutationAssessor	Benign	1.9	M;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-5.7	D;D;D;D
REVEL	Pathogenic	0.80
Sift	Uncertain	0.0040	D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		1.0	D;D;.;.
Vest4		0.61
MutPred		0.43		Loss of disorder (P = 0.0238);.;.;.;
MVP		0.94
MPC		0.12
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.63
gMVP		0.82

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-20029108;