Genetic Variant ITM2A:p.Val202Val (chrX-79361426-C-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_004867.5(ITM2A):c.606G>A(p.Val202Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00861 in 1,205,178 control chromosomes in the GnomAD database, including 37 homozygotes. There are 3,257 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0062 ( 2 hom., 191 hem., cov: 23)

Exomes 𝑓: 0.0089 ( 35 hom. 3066 hem. )

Consequence

ITM2A
NM_004867.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.28

Variant links:

Genes affected

ITM2A (HGNC:6173): (integral membrane protein 2A) This gene encodes a type II membrane protein that belongs to the ITM2 family. Studies in mouse suggest that it may be involved in osteo- and chondrogenic differentiation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

ITM2A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant X-79361426-C-T is Benign according to our data. Variant chrX-79361426-C-T is described in ClinVar as [Benign]. Clinvar id is 769489.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-79361426-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.28 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITM2A	NM_004867.5 link	c.606G>A	p.Val202Val	synonymous_variant	Exon 5 of 6	ENST00000373298.7	NP_004858.1	O43736-1
ITM2A	NM_001171581.2 link	c.474G>A	p.Val158Val	synonymous_variant	Exon 4 of 5		NP_001165052.1	O43736-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ITM2A	ENST00000373298.7 link	c.606G>A	p.Val202Val	synonymous_variant	Exon 5 of 6	1	NM_004867.5	ENSP00000362395.2	O43736-1
ITM2A	ENST00000434584.2 link	c.474G>A	p.Val158Val	synonymous_variant	Exon 4 of 5	2		ENSP00000415533.2	O43736-2
ITM2A	ENST00000469541.5 link	n.566G>A		non_coding_transcript_exon_variant	Exon 5 of 6	2

Frequencies

GnomAD3 genomes

AF:

0.00623

AC:

700

AN:

112304

Hom.:

Cov.:

AF XY:

0.00553

AC XY:

191

AN XY:

34508

show subpopulations

Gnomad AFR

AF:

0.00129

Gnomad AMI

AF:

0.00146

Gnomad AMR

AF:

0.00424

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00255

Gnomad FIN

AF:

0.00376

Gnomad MID

AF:

0.00833

Gnomad NFE

AF:

0.0102

Gnomad OTH

AF:

0.00591

GnomAD3 exomes

AF:

0.00662

AC:

1208

AN:

182401

Hom.:

AF XY:

0.00663

AC XY:

444

AN XY:

66997

show subpopulations

Gnomad AFR exome

AF:

0.00122

Gnomad AMR exome

AF:

0.00475

Gnomad ASJ exome

AF:

0.0121

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00440

Gnomad FIN exome

AF:

0.00400

Gnomad NFE exome

AF:

0.00987

Gnomad OTH exome

AF:

0.00491

GnomAD4 exome

AF:

0.00886

AC:

9682

AN:

1092821

Hom.:

Cov.:

AF XY:

0.00855

AC XY:

3066

AN XY:

358457

show subpopulations

Gnomad4 AFR exome

AF:

0.00110

Gnomad4 AMR exome

AF:

0.00487

Gnomad4 ASJ exome

AF:

0.0132

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00494

Gnomad4 FIN exome

AF:

0.00360

Gnomad4 NFE exome

AF:

0.0101

Gnomad4 OTH exome

AF:

0.00738

GnomAD4 genome

AF:

0.00623

AC:

700

AN:

112357

Hom.:

Cov.:

AF XY:

0.00552

AC XY:

191

AN XY:

34571

show subpopulations

Gnomad4 AFR

AF:

0.00129

Gnomad4 AMR

AF:

0.00423

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00256

Gnomad4 FIN

AF:

0.00376

Gnomad4 NFE

AF:

0.0102

Gnomad4 OTH

AF:

0.00584

Alfa

AF:

0.00824

Hom.:

Bravo

AF:

0.00619

EpiCase

AF:

0.0119

EpiControl

AF:

0.0116

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

1.3

DANN

Benign

0.59

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