X-20015281-C-T

Variant names:

• chrX-20015281-C-T
• rs774928077
• NM_001168465.2:c.1691G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001168465.2(MAP7D2):​c.1691G>A​(p.Arg564His) variant causes a missense change. The variant allele was found at a frequency of 0.0000215 in 1,209,468 control chromosomes in the GnomAD database, including 1 homozygotes. There are 6 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R564S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., 2 hem., cov: 24)
  • Exomes 𝑓: 0.000020 (1 hom. 4 hem.)
• Consequence: MAP7D2 NM_001168465.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.21
• Publications: 5 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 -4 ACMG points.

• BS2: High Hemizygotes in GnomAd4 at 2 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.1691G>A	p.Arg564His	missense	Exon 12 of 17	NP_001161937.1	Q96T17-2
	MAP7D2	NM_152780.4		c.1568G>A	p.Arg523His	missense	Exon 11 of 16	NP_689993.2	Q96T17-1
	MAP7D2	NM_001168466.2		c.1433G>A	p.Arg478His	missense	Exon 10 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.1691G>A	p.Arg564His	missense	Exon 12 of 17	ENSP00000368964.5	Q96T17-2
	MAP7D2	ENST00000379651.7	TSL:1	c.1568G>A	p.Arg523His	missense	Exon 11 of 16	ENSP00000368972.3	Q96T17-1
	MAP7D2	ENST00000970014.1		c.1766G>A	p.Arg589His	missense	Exon 13 of 18	ENSP00000640074.1

Frequencies

GnomAD3 genomes AF: 0.0000358 AC: 4 AN: 111844 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000379

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000656 AC: 12 AN: 183057 AF XY: 0.0000296

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000401

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000200 AC: 22 AN: 1097624 Hom.: 1 Cov.: 29 AF XY: 0.0000110 AC XY: 4 AN XY: 363012

African (AFR) AF: 0.00 AC: 0 AN: 26395

American (AMR) AF: 0.000426 AC: 15 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19383

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30205

South Asian (SAS) AF: 0.00 AC: 0 AN: 54137

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40317

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 0.00000475 AC: 4 AN: 841781

Other (OTH) AF: 0.0000434 AC: 2 AN: 46068

GnomAD4 genome AF: 0.0000358 AC: 4 AN: 111844 Hom.: 0 Cov.: 24 AF XY: 0.0000588 AC XY: 2 AN XY: 34002

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30736

American (AMR) AF: 0.000379 AC: 4 AN: 10545

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3581

South Asian (SAS) AF: 0.00 AC: 0 AN: 2666

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6053

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53188

Other (OTH) AF: 0.00 AC: 0 AN: 1505

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.00000824 AC: 1

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	0.16
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.38	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		5.2
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.65
MutPred		0.59		Loss of MoRF binding (P = 0.0079)
MVP		0.65
MPC		0.15
ClinPred		0.80	D
GERP RS		4.7
Varity_R		0.72
gMVP		0.071
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: rs774928077; hg19: chrX-20033399; COSMIC: COSV65530773; COSMIC: COSV65530773;