X-20010951-C-T

Variant names:

• chrX-20010951-C-T
• rs761523374
• NM_001168465.2:c.2174G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001168465.2(MAP7D2):​c.2174G>A​(p.Arg725Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000761 in 1,208,953 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., 3 hem., cov: 23)
  • Exomes 𝑓: 0.000072 (0 hom. 18 hem.)
• Consequence: MAP7D2 NM_001168465.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.83
• Publications: 3 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.117388636).
• BS2: High Hemizygotes in GnomAd4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001168465.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP7D2	NM_001168465.2	MANE Select	c.2174G>A	p.Arg725Gln	missense	Exon 16 of 17	NP_001161937.1	Q96T17-2
	MAP7D2	NM_152780.4		c.2051G>A	p.Arg684Gln	missense	Exon 15 of 16	NP_689993.2	Q96T17-1
	MAP7D2	NM_001168466.2		c.1916G>A	p.Arg639Gln	missense	Exon 14 of 15	NP_001161938.1	Q96T17-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP7D2	ENST00000379643.10	TSL:1 MANE Select	c.2174G>A	p.Arg725Gln	missense	Exon 16 of 17	ENSP00000368964.5	Q96T17-2
	MAP7D2	ENST00000379651.7	TSL:1	c.2051G>A	p.Arg684Gln	missense	Exon 15 of 16	ENSP00000368972.3	Q96T17-1
	MAP7D2	ENST00000970014.1		c.2249G>A	p.Arg750Gln	missense	Exon 17 of 18	ENSP00000640074.1

Frequencies

GnomAD3 genomes AF: 0.000117 AC: 13 AN: 110910 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000193

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000170

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000189

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000600 AC: 11 AN: 183412 AF XY: 0.0000737

Gnomad AFR exome AF: 0.0000760

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000719 AC: 79 AN: 1097987 Hom.: 0 Cov.: 30 AF XY: 0.0000495 AC XY: 18 AN XY: 363353

African (AFR) AF: 0.0000379 AC: 1 AN: 26397

American (AMR) AF: 0.00 AC: 0 AN: 35202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19384

East Asian (EAS) AF: 0.00 AC: 0 AN: 30197

South Asian (SAS) AF: 0.00 AC: 0 AN: 54134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4116

European-Non Finnish (NFE) AF: 0.0000784 AC: 66 AN: 841947

Other (OTH) AF: 0.000260 AC: 12 AN: 46088

GnomAD4 genome AF: 0.000117 AC: 13 AN: 110966 Hom.: 0 Cov.: 23 AF XY: 0.0000903 AC XY: 3 AN XY: 33216

African (AFR) AF: 0.00 AC: 0 AN: 30465

American (AMR) AF: 0.000192 AC: 2 AN: 10391

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2645

East Asian (EAS) AF: 0.00 AC: 0 AN: 3538

South Asian (SAS) AF: 0.00 AC: 0 AN: 2607

European-Finnish (FIN) AF: 0.000170 AC: 1 AN: 5882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.000189 AC: 10 AN: 53030

Other (OTH) AF: 0.00 AC: 0 AN: 1510

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000756

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.000218

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.055	T
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.12	T
MetaSVM	Uncertain	0.26	D
MutationAssessor	Benign	0.55	N
PhyloP100		1.8
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.25
Sift	Benign	0.23	T
Sift4G	Benign	0.29	T
Polyphen		1.0	D
Vest4		0.17
MVP		0.81
MPC		0.14
ClinPred		0.10	T
GERP RS		3.3
Varity_R		0.10
gMVP		0.44
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs761523374; hg19: chrX-20029069; COSMIC: COSV65525629;