2-216482470-G-A

Position:

• chr2-216482470-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014140.4(SMARCAL1):​c.2626-268G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 152,212 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.026 (73 hom., cov: 32)
• Consequence: SMARCAL1 NM_014140.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.223

Genes affected

SMARCAL1 (HGNC:11102): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a like 1) The protein encoded by this gene is a member of the SWI/SNF family of proteins. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein shows sequence similarity to the E. coli RNA polymerase-binding protein HepA. Mutations in this gene are a cause of Schimke immunoosseous dysplasia (SIOD), an autosomal recessive disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction, and T-cell immunodeficiency. [provided by RefSeq, Jul 2008]

RPL37A-DT (HGNC:40510): (RPL37A divergent transcript)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-216482470-G-A is Benign according to our data. Variant chr2-216482470-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1203234.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCAL1	NM_014140.4	c.2626-268G>A		intron_variant		ENST00000357276.9	NP_054859.2
SMARCAL1	NM_001127207.2	c.2626-268G>A		intron_variant			NP_001120679.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCAL1	ENST00000357276.9	c.2626-268G>A		intron_variant		2	NM_014140.4	ENSP00000349823	P1
RPL37A-DT	ENST00000453157.1	n.283-3211C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0260 AC: 3947 AN: 152094 Hom.: 73 Cov.: 32

Gnomad AFR AF: 0.00683

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0249

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0570

Gnomad FIN AF: 0.0209

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0349

Gnomad OTH AF: 0.0249

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0259 AC: 3947 AN: 152212 Hom.: 73 Cov.: 32 AF XY: 0.0256 AC XY: 1906 AN XY: 74406

Gnomad4 AFR AF: 0.00681

Gnomad4 AMR AF: 0.0248

Gnomad4 ASJ AF: 0.0965

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0573

Gnomad4 FIN AF: 0.0209

Gnomad4 NFE AF: 0.0349

Gnomad4 OTH AF: 0.0247

Alfa AF: 0.0340 Hom.: 18

Bravo AF: 0.0248

Asia WGS AF: 0.0190 AC: 66 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 01, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.39

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

Other links and lift over

dbSNP: rs116315714; hg19: chr2-217347193;