X-20016108-T-C

Position:

• chrX-20016108-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001168465.2(MAP7D2):​c.1630A>G​(p.Met544Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,096,359 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000027 (0 hom. 2 hem.)
• Consequence: MAP7D2 NM_001168465.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.427

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07032615).
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP7D2	NM_001168465.2	c.1630A>G	p.Met544Val	missense_variant	11/17	ENST00000379643.10	NP_001161937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP7D2	ENST00000379643.10	c.1630A>G	p.Met544Val	missense_variant	11/17	1	NM_001168465.2	ENSP00000368964	A2
MAP7D2	ENST00000379651.7	c.1507A>G	p.Met503Val	missense_variant	10/16	1		ENSP00000368972	A2
MAP7D2	ENST00000443379.7	c.1372A>G	p.Met458Val	missense_variant	9/15	2		ENSP00000388239	A2
MAP7D2	ENST00000452324.3	c.1351A>G	p.Met451Val	missense_variant	10/16	2		ENSP00000413301	P2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000274 AC: 3 AN: 1096359 Hom.: 0 Cov.: 30 AF XY: 0.00000553 AC XY: 2 AN XY: 361821

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000285

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: 0.00000238

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

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

Apr 29, 2024

The c.1630A>G (p.M544V) alteration is located in exon 11 (coding exon 11) of the MAP7D2 gene. This alteration results from a A to G substitution at nucleotide position 1630, causing the methionine (M) at amino acid position 544 to be replaced by a valine (V). 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	0.062
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.7
DANN	Benign	0.80
DEOGEN2	Benign	0.051	T;.;.;.
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.52	T;T;T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.070	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.3	N;N;N;N
REVEL	Benign	0.049
Sift	Benign	0.52	T;T;T;T
Sift4G	Benign	0.59	T;T;T;T
Polyphen		0.0010	B;B;.;.
Vest4		0.16
MutPred		0.56		Gain of ubiquitination at K501 (P = 0.1115);.;.;.;
MVP		0.15
MPC		0.12
ClinPred		0.027	T
GERP RS		-2.1
Varity_R		0.085
gMVP		0.012

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

Other links and lift over

dbSNP: rs2073378461; hg19: chrX-20034226;