Variant X-20012470-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000379643.10(MAP7D2):c.1951C>T(p.Pro651Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000897 in 1,204,473 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 40 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 3 hem., cov: 22)

Exomes 𝑓: 0.000086 ( 0 hom. 37 hem. )

Consequence

MAP7D2
ENST00000379643.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01

Variant links:

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]

MAP7D2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06629437).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP7D2	NM_001168465.2 linkuse as main transcript	c.1951C>T	p.Pro651Ser	missense_variant	15/17	ENST00000379643.10	NP_001161937.1	Q96T17-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MAP7D2	ENST00000379643.10 linkuse as main transcript	c.1951C>T	p.Pro651Ser	missense_variant	15/17	1	NM_001168465.2	ENSP00000368964.5	Q96T17-2
MAP7D2	ENST00000379651.7 linkuse as main transcript	c.1828C>T	p.Pro610Ser	missense_variant	14/16	1		ENSP00000368972.3	Q96T17-1
MAP7D2	ENST00000443379.7 linkuse as main transcript	c.1693C>T	p.Pro565Ser	missense_variant	13/15	2		ENSP00000388239.3	Q96T17-4
MAP7D2	ENST00000452324.3 linkuse as main transcript	c.1672C>T	p.Pro558Ser	missense_variant	14/16	2		ENSP00000413301.3	Q96T17-5

Frequencies

GnomAD3 genomes

AF:

0.000126

AC:

AN:

110703

Hom.:

Cov.:

AF XY:

0.0000903

AC XY:

AN XY:

33239

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000100

AC:

AN:

179265

Hom.:

AF XY:

0.0000782

AC XY:

AN XY:

63947

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000627

Gnomad NFE exome

AF:

0.000210

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000859

AC:

AN:

1093770

Hom.:

Cov.:

AF XY:

0.000103

AC XY:

AN XY:

359586

show subpopulations

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:

0.0000741

Gnomad4 NFE exome

AF:

0.000106

Gnomad4 OTH exome

AF:

0.0000435

GnomAD4 genome

AF:

0.000126

AC:

AN:

110703

Hom.:

Cov.:

AF XY:

0.0000903

AC XY:

AN XY:

33239

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000377

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000988

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 11, 2023

The c.1951C>T (p.P651S) alteration is located in exon 15 (coding exon 15) of the MAP7D2 gene. This alteration results from a C to T substitution at nucleotide position 1951, causing the proline (P) at amino acid position 651 to be replaced by a serine (S). 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

0.076

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.057

T;.;.;.

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.78

T;T;T;T

M_CAP

Benign

0.0053

MetaRNN

Benign

0.066

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.1

N;N;N;N

REVEL

Benign

0.042

Sift

Benign

0.19

T;T;T;T

Sift4G

Benign

0.48

T;T;T;T

Polyphen

0.71

P;P;.;.

Vest4

0.15

MutPred

0.29

Gain of disorder (P = 0.1752);.;.;.;

MVP

0.10

MPC

0.12

ClinPred

0.068

GERP RS

3.2

Varity_R

0.12

gMVP

0.44

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over