X-20012356-C-T

Position:

• chrX-20012356-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000379643.10(MAP7D2):​c.2065G>A​(p.Asp689Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000461 in 1,083,892 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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: 0.0000046 (0 hom. 3 hem.)
• Consequence: MAP7D2 ENST00000379643.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.84

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP7D2	NM_001168465.2	c.2065G>A	p.Asp689Asn	missense_variant	15/17	ENST00000379643.10	NP_001161937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP7D2	ENST00000379643.10	c.2065G>A	p.Asp689Asn	missense_variant	15/17	1	NM_001168465.2	ENSP00000368964.5
MAP7D2	ENST00000379651.7	c.1942G>A	p.Asp648Asn	missense_variant	14/16	1		ENSP00000368972.3
MAP7D2	ENST00000443379.7	c.1807G>A	p.Asp603Asn	missense_variant	13/15	2		ENSP00000388239.3
MAP7D2	ENST00000452324.3	c.1786G>A	p.Asp596Asn	missense_variant	14/16	2		ENSP00000413301.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000461 AC: 5 AN: 1083892 Hom.: 0 Cov.: 28 AF XY: 0.00000855 AC XY: 3 AN XY: 350954

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: 0.00000600

Gnomad4 OTH exome AF: 0.00

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

Aug 28, 2023

The c.2065G>A (p.D689N) alteration is located in exon 15 (coding exon 15) of the MAP7D2 gene. This alteration results from a G to A substitution at nucleotide position 2065, causing the aspartic acid (D) at amino acid position 689 to be replaced by an asparagine (N). 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	Pathogenic	0.77
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.32	T;.;.;.
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.39	T;T;T;T
MetaSVM	Uncertain	0.55	D
MutationAssessor	Uncertain	2.1	M;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.2	N;N;D;N
REVEL	Uncertain	0.44
Sift	Uncertain	0.0080	D;D;D;D
Sift4G	Uncertain	0.034	D;D;D;D
Polyphen		1.0	D;D;.;.
Vest4		0.41
MutPred		0.30		Loss of phosphorylation at S650 (P = 0.1387);.;.;.;
MVP		0.86
MPC		0.12
ClinPred		0.91	D
GERP RS		5.5
Varity_R		0.46
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.33		Position offset: -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-20030474;