NM_001168465.2:c.2065G>A

Variant names:

• chrX-20012356-C-T
• NM_001168465.2:c.2065G>A

Variant summary

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

The NM_001168465.2(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 NM_001168465.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.84
• Publications: 0 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 GnomAdExome4 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.2065G>A	p.Asp689Asn	missense	Exon 15 of 17	NP_001161937.1	Q96T17-2
	MAP7D2	NM_152780.4		c.1942G>A	p.Asp648Asn	missense	Exon 14 of 16	NP_689993.2	Q96T17-1
	MAP7D2	NM_001168466.2		c.1807G>A	p.Asp603Asn	missense	Exon 13 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.2065G>A	p.Asp689Asn	missense	Exon 15 of 17	ENSP00000368964.5	Q96T17-2
	MAP7D2	ENST00000379651.7	TSL:1	c.1942G>A	p.Asp648Asn	missense	Exon 14 of 16	ENSP00000368972.3	Q96T17-1
	MAP7D2	ENST00000970014.1		c.2140G>A	p.Asp714Asn	missense	Exon 16 of 18	ENSP00000640074.1

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

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

African (AFR) AF: 0.00 AC: 0 AN: 26063

American (AMR) AF: 0.00 AC: 0 AN: 33887

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18932

East Asian (EAS) AF: 0.00 AC: 0 AN: 29925

South Asian (SAS) AF: 0.00 AC: 0 AN: 51488

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4039

European-Non Finnish (NFE) AF: 0.00000600 AC: 5 AN: 833621

Other (OTH) AF: 0.00 AC: 0 AN: 45585

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 23

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	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
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.39	T
MetaSVM	Uncertain	0.55	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.8
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.44
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.034	D
Polyphen		1.0	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
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

hg19: chrX-20030474;